Miembros del Grupo
Coordinador
Investigadores
Colaboradores
Líneas de Investigación
- Aplicación clínica de distintos métodos de biopsia líquida en cáncer.
- Combinación de agentes en inmunoterapia del cáncer y marcadores predictivos de respuesta.
- Estudio de biomarcadores de resistencia al tratamiento oncológico y nuevas dianas terapéuticas.
- Mecanismos de metástasis.
- Mecanismos de resistencia a terapias dirigidas en cáncer de pulmón.
- Modelos animales de metástasis.
Palabras Clave
- Biomarcadores predistivos
- Biopsia líquida en tumores sólidos
- Inmunoterapia
- Mecanismos de metástasis
- Mecanismos de resistencia
Publicaciones Científicas desde 2018
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Autores: Maroto Garcia, Julia; Deza Casquero, Sara; Fuentes Bullejos, Patricia; et al.Revista: DIAGNOSISISSN: 2194-802X Vol.10 N° 3 2023 págs. 281 - 297ResumenObjectives: Remote self-collected capillary blood samples have been proposed as alternative to venous blood samples as an aid in telemedicine. The aim of this work is to compare the preanalytical and analytical performance of these two types of samples and to study the stability of common measurands in capillary blood. Methods: Capillary and venous blood samples were collected in parallel from 296 patients in serum tubes to analyze 22 common biochemistry magnitudes after centrifugation and in EDTA tubes to analyze 15 hematologic magnitudes. Quality of the preanalytical process was assessed applying the model of quality indicator. 24 h stability at room temperature was studied by obtaining paired capillary samples. A questionnaire of assessment was conducted. Results: Mean hemolysis index was higher in capillary samples compared to venous blood samples (p<0.001). Regression analysis and difference analysis showed no bias for all studied biochemistry parameters and hematologic parameters, except mean corpuscular volume (MCV), between capillary and venous blood samples. Regarding sample stability, percentage deviation was higher than the corresponding minimum analytical performance specification for ferritin, vitamin D, hematocrit, MCV, mean corpuscular hemoglobin concentration, platelets distribution wide, mean platelet volume and basophils. Finger pricking was perceived as less painful (p<0.05) than venipuncture in participants who undergo more than one blood test per year. Conclusions: Capillary blood can be used as an alternative to venous blood for the studied parameters in automated common clinical analyzers. Cautious should be taken if samples are not analyzed within 24 h from the collection.
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Autores: Erice Azparren, Oihane; Narayanan, S.; Feliu, I.; et al.Título: LAMC2 regulates key transcriptional and targetable effectors to support pancreatic cancer growthRevista: CLINICAL CANCER RESEARCHISSN: 1078-0432 Vol.29 N° 6 2023 págs. 1137 - 1154ResumenPurpose: The identification of pancreatic ductal adenocarcino-ma (PDAC) dysregulated genes may unveil novel molecular targets entering inhibitory strategies. Laminins are emerging as potential targets in PDAC given their role as diagnostic and prognostic markers. Here, we investigated the cellular, functional, and clinical relevance of LAMC2 and its regulated network, with the ultimate goal of identifying potential therapies. Experimental Design: LAMC2 expression was analyzed in PDAC tissues, a panel of human and mouse cell lines, and a genetically engineered mouse model. Genetic perturbation in 2D, 3D, and in vivo allograft and xenograft models was done. Expression profiling of a LAMC2 network was performed by RNA-sequencing, and publicly available gene expression datasets from experimental and clinical studies examined to query its human relevance. Dual inhibition of pharmacologically targetable LAMC2-regulated effec-tors was investigated. Results: LAMC2 was consistently upregulated in human and mouse experimental models as well as in human PDAC specimens, and associated with tumor grade and survival. LAMC2 inhibition impaired cell cycle, induced apoptosis, and sensitized PDAC to MEK1/2 inhibitors (MEK1/2i). A LAMC2-regulated network was featured in PDAC, including both classical and quasi-mesenchymal subtypes, and contained downstream effectors transcriptionally shared by the KRAS signaling pathway. LAMC2 regulated a func-tional FOSL1-AXL axis via AKT phosphorylation. Furthermore, genetic LAMC2 or pharmacological AXL inhibition elicited a synergistic antiproliferative effect in combination with MEK1/2is that was consistent across 2D and 3D human and mouse PDAC models, including primary patient-derived organoids. Conclusions: LAMC2 is a molecular target in PDAC that regulates a transcriptional network that unveils a dual drug com-bination for cancer treatment.
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Autores: Caballé, I.; Buño, A.; Bernabeu , F. A.; et al.Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIOISSN: 2628-491X Vol.4 N° 1 2023 págs. 70 - 80ResumenObjectives Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals. Methods The Spanish Society of Laboratory Medicine distributed a questionnaire among the 250 most representative centers (the ones with the largest volume of determinations and training programs), of which 174 (69.6%) returned the questionnaire providing data for 2019. Results Laboratories were classified according to the number of determinations. In total, 37% identified themselves as small (<1 million determinations per year); 40% considered themselves medium-sized (1¿5 million determinations per year) and 23% considered they were large laboratories (>5 million determinations). The level of specialization of laboratory physicians and laboratory performance were higher in large laboratories. Most requests (87%) and determinations (93%) corresponded to biochemistry and hematology. As many as 63% of physicians had an indefinite contract, and 23% were older than 60 years. Conclusions Laboratory medicine is a consolidated discipline that is gaining relevance in Spain. It adds value to the diagnosis, prognosis and follow-up of diseases, and to treatment response monitoring. The results of this study will help us address challenges such as the need for specialized training for laboratory professionals; the emergence of technological innovations; exploitation of Big Data; optimization of quality management systems and patient safety.
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Autores: Deza Casquero, Sara; Maroto Garcia, Julia; Tellechea, O.; et al.Revista: CLINICA CHIMICA ACTAISSN: 0009-8981 Vol.548 2023 págs. 117502ResumenBackground and aims: Patients' response to treatment in differentiated thyroid cancer (DTC) is classified according to serum thyroglobulin concentrations (Tg), usually using the American Thyroid Association guidelines and considering potential interfering anti-thyroglobulin antibodies (Ab-Tg). We aim to evaluate the clinical implications of changing Tg and Ab-Tg quantification method. Material and methods: Tg and Ab-Tg were quantified in 82 serum samples (60 from DTC patients) by Elecsys and Access immunoassays. Results: Elecsys immunoassay rendered higher values of Tg than Access: mean bias 5.03 ng/mL (95%CI:-14.14-24.21). In DTC patients, there was an almost perfect agreement for response classification (kappa index=0.833). Discrepancies appeared in patients with undetermined response, with a more tendency to subclassification with Access. Ab-Tg showed a poor correlation (r=0.5394). When Elecsys cut-off was reduced to 43 IU/mL, agreement for positive/negative classification improved from a kappa index of 0.607 to 0.650. Prospective study with personalized follow-up showed that only 6.3% of Tg results required an analytical confirmation, being confirmed 93% of them. Conclusions: Despite the biases observed, clinical impact of an analytical change is minimal in patients' management. However, cautious and personalized follow-up period after the change is still mandatory, especially in patients with Tg levels between 0.2 and 1 ng/mL.
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Autores: Lopez-Borrego, S.; Campos-Silva, C.; Sandua Condado, Amaia; et al.Revista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGYISSN: 2296-634X Vol.10 2023 págs. 1055288ResumenMetastatic melanoma presents, in many cases, oncogenic mutations in BRAF, a MAPK involved in proliferation of tumour cells. BRAF inhibitors, used as therapy in patients with these mutations, often lead to tumour resistance and, thus, the use of MEK inhibitors was introduced in clinics. BRAFi/MEKi, a combination that has modestly increased overall survival in patients, has been proven to differentially affect immune ligands, such as NKG2D-ligands, in drug-sensitive vs. drug-resistant cells. However, the fact that NKG2D-ligands can be released as soluble molecules or in extracellular vesicles represents an additional level of complexity that has not been explored. Here we demonstrate that inhibition of MAPK using MEKi, and the combination of BRAFi with MEKi in vitro, modulates NKG2D-ligands in BRAF-mutant and WT melanoma cells, together with other NK activating ligands. These observations reinforce a role of the immune system in the generation of resistance to directed therapies and support the potential benefit of MAPK inhibition in combination with immunotherapies. Both soluble and EV-associated NKG2D-ligands, generally decreased in BRAF-mutant melanoma cell supernatants after MAPKi in vitro, replicating cell surface expression. Because potential NKG2D-ligand fluctuation during MAPKi treatment could have different consequences for the immune response, a pilot study to measure NKG2D-ligand variation in plasma or serum from metastatic melanoma patients, at different time points during MAPKi treatment, was performed. Not all NKG2D-ligands were equally detected. Further, EV detection did not parallel soluble protein. Altogether, our data confirm the heterogeneity between melanoma lesions, and suggest testing several NKG2D-ligands and other melanoma antigens in serum, both as soluble or vesicle-released proteins, to help classifying immune competence of patients.
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Autores: Vilalta Lacarra, Anna; Aldaz Pastor, Azucena; Sala Elarre, Pablo; et al.Título: Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinomaRevista: PANCREATOLOGYISSN: 1424-3903 Vol.23 N° 4 2023 págs. 411 - 419ResumenBackground: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer. Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated. Results: By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU area under the curve (AUC) above 28 mcg·h/mL or CPT-11 AUC values below 10 mcg·h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC ¿28 mcg·h/mL [HR = 0.251, 95% CI 0.096-0.656; p = 0.005] and CPT-11 AUC <10 mcg·h/mL [HR = 0.189, 95% CI 0.073-0.486, p = 0.001]. Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic ductal adenocarcinoma.
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Autores: Farina, B. (Autor de correspondencia); Ramos-Guerra, A. D.; Bermejo-Peláez, D.; et al.Revista: JOURNAL OF TRANSLATIONAL MEDICINEISSN: 1479-5876 Vol.21 N° 1 2023 págs. 174ResumenBackgroundIdentifying predictive non-invasive biomarkers of immunotherapy response is crucial to avoid premature treatment interruptions or ineffective prolongation. Our aim was to develop a non-invasive biomarker for predicting immunotherapy clinical durable benefit, based on the integration of radiomics and clinical data monitored through early anti-PD-1/PD-L1 monoclonal antibodies treatment in patients with advanced non-small cell lung cancer (NSCLC).MethodsIn this study, 264 patients with pathologically confirmed stage IV NSCLC treated with immunotherapy were retrospectively collected from two institutions. The cohort was randomly divided into a training (n = 221) and an independent test set (n = 43), ensuring the balanced availability of baseline and follow-up data for each patient. Clinical data corresponding to the start of treatment was retrieved from electronic patient records, and blood test variables after the first and third cycles of immunotherapy were also collected. Additionally, traditional radiomics and deep-radiomics features were extracted from the primary tumors of the computed tomography (CT) scans before treatment and during patient follow-up. Random Forest was used to implementing baseline and longitudinal models using clinical and radiomics data separately, and then an ensemble model was built integrating both sources of information.ResultsThe integration of longitudinal clinical and deep-radiomics data significantly improved clinical durable benefit prediction at 6 and 9 months after treatment in the independent test set, achieving an area under the receiver operating characteristic curve of 0.824 (95% CI: [0.658,0.953]) and 0.753 (95% CI: [0.549,0.931]). The Kaplan-Meier survival analysis showed that, for both endpoints, the signatures significantly stratified high- and low-risk patients (p-value< 0.05) and were significantly correlated with progression-free survival (PFS6 model: C-index 0.723, p-value = 0.004; PFS9 model: C-index 0.685, p-value = 0.030) and overall survival (PFS6 models: C-index 0.768, p-value = 0.002; PFS9 model: C-index 0.736, p-value = 0.023).ConclusionsIntegrating multidimensional and longitudinal data improved clinical durable benefit prediction to immunotherapy treatment of advanced non-small cell lung cancer patients. The selection of effective treatment and the appropriate evaluation of clinical benefit are important for better managing cancer patients with prolonged survival and preserving quality of life.
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Autores: Caglevic, C. (Autor de correspondencia); Rolfo, C.; Gil Bazo, Ignacio; et al.Revista: JCO GLOBAL ONCOLOGYISSN: 2687-8941 Vol.8 2022 págs. e2200123ResumenOn February 24, 2022, a war began within the Ukrainian borders. At least 3.0 million Ukrainian inhabitants have already fled the country. Critical infrastructure, including hospitals, has been damaged. Children with cancer were urgently transported to foreign countries, in an effort to minimize interruption of their life-saving treatments. Most adults did not have that option. War breeds cancer-delaying diagnosis, preventing treatment, and increasing risk. We project that a modest delay in care of only 4 months for five prevalent types of cancer will lead to an excess of over 3,600 cancer deaths in the subsequent years. It is critical that we establish plans to mitigate that risk as soon as possible.
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Autores: Alegre Martínez, Estíbaliz (Autor de correspondencia); Casal de Andrés, Henar; Galofre Ferrater, Juan Carlos; et al.Revista: CLINICAL CHEMISTRYISSN: 0009-9147 Vol.68 N° 9 2022 págs. 1128 - 1132
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Autores: González Hernández, Álvaro (Autor de correspondencia); Maroto Garcia, Julia; Varo Cenarruzabeitia, NereaRevista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIOISSN: 2628-491X Vol.3 N° 4 2022 págs. 317 - 318
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Autores: Lasierra-Monclús, A. B.; González Hernández, Álvaro (Autor de correspondencia); Bernabéu-Andreu, F. A.; et al.Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIOISSN: 2628-491X Vol.3 N° 4 2022 págs. 361 - 370ResumenObjectives: To assess the impact of the COVID-19 pandemic on the activity of clinical laboratories in Spain.Methods: A descriptive, observational, retrospective, multicenter study.Results: Between March and December 2020, there was a statistically significant decrease in the number of test requests (-17.7%, p=< 0.001) and total tests performed (-18.3%, p < 0.001) with respect to the same period in 2019. A decrease was observed in the number of requests from primary care (-37.4%) (p < 0.001) and in the number of foecal occult blood (-45.8%); qualitative urine (-30.1%); PSA (-28.5%); TSH (-27.8%); total cholesterol (-27.2%) and HbA(1c) (-24.7%) tests performed, p < 0.001. A significant increase was found in the number of requests from ICUs (76.6%, p < 0.001) and number of IL-6 (+22,350.9), D-dimer (+617.2%), troponin (+46.8%) and arterial blood gas (+3.9%) tests carried out, p < 0.001. During the first months of 2021, there were significant changes in the number of requests for qualitative urine (-8.7%, p < 0.001), PSA (-6.3%, p=0.009), IL-6 (+66,269.2, p < 0.001), D-dimer (+603.6%, p < 0.001), troponin (+28.7%, p < 0.001), arterial blood gas (+26,2%, p=0.014) and ferritin (+16.0%, p=0.002) tests performed.Conclusions: There were changes in the origin and number of test requested to clinical laboratories in Spain. The number of requests for the evaluation and monitoring of COVID-19 patients increased, whereas requests for the control of non-COVID patients and for population screening decreased. Long-term analysis reveals that the volume of tests performed for the control of chronic diseases returned to normal over time, whereas the increase observed in the volume of tests performed for the management of COVID-19 patients is maintained.
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Autores: Campos-Silva, C.; Cáceres-Martell, Y.; Sánchez-Herrero, E.; et al.Título: A simple immunoassay for extracellular vesicle liquid biopsy in microliters of non-processed plasmaRevista: JOURNAL OF NANOBIOTECHNOLOGYISSN: 1477-3155 Vol.20 N° 1 2022 págs. 72ResumenBackground: Extracellular vesicles (EVs), released by most cell types, provide an excellent source of biomarkers in biological fluids. However, in order to perform validation studies and screenings of patient samples, it is still necessary to develop general techniques permitting rapid handling of small amounts of biological samples from large numbers of donors. Results: Here we describe a method that, using just a few microliters of patient's plasma, identifies tumour markers exposed on EVs. Studying physico-chemical properties of EVs in solution, we demonstrate that they behave as stable colloidal suspensions and therefore, in immunocapture assays, many of them are unable to interact with a stationary functionalised surface. Using flocculation methods, like those used to destabilize colloids, we demonstrate that cationic polymers increase EV zeta-potential, diameter, and sedimentation coefficient and thus, allow a more efficient capture on antibody-coated surfaces by both ELISA and bead-assisted flow cytometry. These findings led to optimization of a protocol in microtiter plates allowing effective immunocapture of EVs, directly in plasma without previous ultracentrifugation or other EV enrichment. The method, easily adaptable to any laboratory, has been validated using plasma from lung cancer patients in which the epithelial cell marker EpCAM has been detected on EVs. Conclusions: This optimized high throughput, easy to automate, technology allows screening of large numbers of patients to phenotype tumour markers in circulating EVs, breaking barriers for the validation of proposed EV biomarkers and the discovery of new ones.
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Autores: Alegre Martínez, Estíbaliz (Autor de correspondencia); Sandua Condado, Amaia; Calleja Aznarez, Sofía; et al.Revista: SCIENTIFIC REPORTSISSN: 2045-2322 Vol.12 N° 1 2022 págs. 9752ResumenBreath tests used to evaluate carbohydrates malabsorption require baseline H2 and CH4 levels as low as possible. Test cancellation is recommended when exceeding certain cut-offs (H2 ¿ 20 ppm and CH4 ¿ 10 ppm). Although following preparation protocols, many patients have baseline levels above those cut-offs. We investigated if light walking can reduce baseline H2 and CH4 levels. We retrospectively analyzed baseline H2 and CH4 levels from 1552 breath tests. Baseline levels (B1), especially in H2, were lower when obtained at later hours of the day. In those with baseline levels above cut-off, re-sampling (B2) after light walking for one hour, decreased H2 levels 8 ppm (Q1-Q3: 1-18 ppm), and 2 ppm (Q1-Q3: 0-3 ppm) for CH4. Consequently, 40% of tests with elevated B1 levels, presented B2 levels below mentioned cut-offs. Ten percent of tests considered negative when using B1 for calculations, turned positive when using B2 instead. All positive tests when using B1 values, remained elevated when using B2. Re-sampling after light walking for one hour could allow test performance in those with previous elevated baseline levels, avoiding diagnosis delays. Using the second sample for delta calculations identifies positive patients for malabsorption that would have been considered negative.
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Autores: Monteiro, C.; Miarka, L.; Perea-García, M.; et al.Revista: NATURE MEDICINEISSN: 1078-8956 Vol.28 N° 4 2022 págs. 752 - 765ResumenA comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy. Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-kappa B-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.
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Autores: Alegre Martínez, Estíbaliz; Varo Cenarruzabeitia, Nerea; Fernandez-Calle, P.; et al.Revista: CLINICAL CHEMISTRY AND LABORATORY MEDICINEISSN: 1434-6621 Vol.60 N° 7 2022 págs. 1003 - 1010ResumenObjectives Retrospective studies frequently assume analytes long-term stability at ultra-low temperatures. However, these storage conditions, common among biobanks and research, may increase the preanalytical variability, adding a potential uncertainty to the measurements. This study is aimed to evaluate long-term storage stability of different analytes at Methods Twenty-one analytes commonly measured in clinical laboratories were quantified in 60 serum samples. Samples were immediately aliquoted and frozen at <-70 degrees C, and reanalyzed after 11 +/- 3.9 years of storage. A change in concentration after storage was considered relevant if the percent deviation from the baseline measurement was significant and higher than the analytical performance specifications. Results Preanalytical variability (CVP) due to storage, determined by the percentage deviation, showed a noticeable dispersion. Changes were relevant for alanine aminotransferase, creatinine, glucose, magnesium, potassium, sodium, total bilirubin and urate. No significant differences were found in aspartate aminotransferase, calcium, carcinoembryonic antigen, cholesterol, C-reactive protein, direct bilirubin, free thryroxine, gamma-glutamyltransferase, lactate dehydrogenase, prostate-specific antigen, triglycerides, thyrotropin, and urea. As nonnegligible, CVP must remain included in reference change value formula, which was modified to consider whether one or two samples were frozen. Conclusions After long-term storage at ultra-low temperatures, there was a significant variation in some analytes that should be considered. We propose that reference change value formula should include the CVP when analyzing samples stored in these conditions.
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Autores: Garcia-del-Muro, X. (Autor de correspondencia); Duran, I.; Pérez Gracia, José Luis; et al.Revista: CLINICAL GENITOURINARY CANCERISSN: 1558-7673 Vol.20 N° 4 2022 págs. 388.e1 - 388.e10ResumenPhase I/II translational trial evaluating the molecular determinants of pazopanib plus interferon alpha efficacy in advanced renal cell carcinoma. The expression levels of TNF-alpha, endoglin and PD-L1 correlated with response at eight weeks after treatment initiation. This suggests a crucial role of vascular remodelling and inflammatory-mediated immune cell infiltration for an optimal response to pazopanib plus interferon alpha combination. Introduction: The therapeutic repertoire available for advanced renal cell carcinoma (RCC), including tyrosine kinase inhibitors (TKIs) and immunotherapy, required for molecular biomarkers for response. Patients and Methods: This was a phase I to II trial on the combination of pazopanib with interferon-alpha (INF-2A) as first-line treatment for advanced RCC. The primary endpoint was recommended phase II dose (RP2D) and efficacy in terms of objective response rate (ORR, RECIST 1.1 criteria). Secondary endpoints included safety and a translational study of molecular biomarkers in serum and exosomes from peripheral blood samples at three-time points: baseline, 8 weeks of treatment, and progression of the disease Results: Between July 2011 and July 2017, 53 eligible patients were treated and followed up (I, n = 20; II, n = 33). Pazopanib 800 mg + INF-2A 3 MIUs showed a manageable safety profile; therefore, it was selected for dose expansion. Overall, grade 3/4 toxicities were reported in 24 (72.7%) patients. The ORR was 27.2%. The 12-month OS rate was 83.6% (median not reached), and after 30.9 months of follow-up, 24 (72.7%) patients were still alive, CCL2, IL8, TNF-alpha, and PD-L1 were significantly overexpressed after treatment initiation, while TGF-beta 1 and CCL5 were significantly decreased. TNF-alpha, endoglin, and PD-L1 expression are correlated with the response after treatment initiation. Conclusion: The trial did not reach its pre-specified target ORR. However, OS was longer than expected with pazopanib monotherapy. Changes in the molecular profile suggest a crucial role of vascular remodeling and infIammatory-mediated immune cell infiltration in optimal response to pazopanib plus INF-2A. (C) 2022 Elsevier Inc. All rights reserved.
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Autores: Szabados, B.; Ponz Sarvisé, Mariano; Machado, R.; et al.Revista: CLINICAL CANCER RESEARCHISSN: 1078-0432 Vol.28 N° 18 2022 págs. 4083 - 4091ResumenPurpose: This retrospective analysis of the largest available clinico-genomic database used de-identified patient-level electronic health record-derived real-world data (RWD) combined with FoundationOne comprehensive genomic profiling (CGP) to characterize patients with metastatic urothelial carcinoma (mUC) treated in the real-world setting, detect potential biomarkers, and develop a bladder immune performance index (BIPI). Experimental design: Patients with mUC who started front-line single-agent immune checkpoint inhibitors (ICI) and an unmatched group treated with front-line platinum-based chemotherapy between January 1, 2011, and September 30, 2019, were selected. Clinical and genomic data were correlated with overall survival (OS). A novel BIPI predicting outcome with ICIs was developed using machine learning methods and validated using data from a phase II trial (NCT02951767). Results: In ICI-treated patients (n = 118), high tumor mutational burden (¿10 mutations/megabase) was associated with improved OS (HR, 0.58; 95% CI, 0.35-0.95; P = 0.03). In chemotherapy-treated patients (n = 268), those with high APOBEC mutational signature had worse OS (HR, 1.43; 95% CI, 1.06-1.94; P = 0.02). Neither FGFR3 mutations nor DNA damage-repair pathway alterations were associated with OS. A novel BIPI combining clinical and genomic variables (nonmetastatic at initial diagnosis, normal or above normal albumin level at baseline, prior surgery for organ-confined disease, high tumor mutational burden) identified ICI-treated patients with longest OS and was validated in an independent dataset. Conclusions: Contemporary RWD including FoundationOne CGP can be used to characterize outcomes in real-world patients according to biomarkers beyond PD-L1. A validated, novel clinico-genomic BIPI demonstrated satisfactory prognostic performance for OS in patients with mUC receiving front-line ICI therapy.
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Autores: Visa, L.; Sauri, T.; Esposito, F.; et al.Título: Comprehensive circulating tumor (ct) DNA NGS for molecular profiling in advanced cholangiocarcinomaRevista: ANNALS OF ONCOLOGYISSN: 0923-7534 Vol.33 N° Supl. 4 2022 págs. S242 - S243
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Autores: Szabados, B.; Ponz Sarvisé, Mariano; Machado, R.; et al.Revista: JOURNAL OF CLINICAL ONCOLOGYISSN: 0732-183X Vol.40 N° 6 2022
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Autores: Schram, A.; Borad, M.; Sahai, V.; et al.Revista: EUROPEAN JOURNAL OF CANCERISSN: 0959-8049 Vol.174 N° SUPPL 1 2022 págs. S116 - S116
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Autores: Izquierdo-Sanchez, L.; Lamarca, A.; La Casta, A.; et al.Revista: JOURNAL OF HEPATOLOGY (ONLINE)ISSN: 0168-8278 Vol.77 N° Supl. 1 2022 págs. S107 - S108
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Autores: Puyalto Calvo, Ander; Rodríguez Remírez, María; López, I.; et al.Revista: ANNALS OF ONCOLOGYISSN: 0923-7534 Vol.33 N° 7 2022 págs. S1327 - S1327
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Autores: Ou, S. H.; Moreno-García, V.; Gil Bazo, Ignacio; et al.Revista: EUROPEAN JOURNAL OF CANCERISSN: 0959-8049 Vol.174 N° SUPPL 1 2022 págs. S122 - S122
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Autores: de Braud, F.; Dooms, C.; Heist, R. S.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
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Autores: Aparicio-Salcedo, I.; Iranzo-Gómez, P.; Reyes, R.; et al.Título: High incidence of peridiagnosis thromboembolic events in patients with BRAF mutant lung cancerRevista: JOURNAL OF THORACIC ONCOLOGYISSN: 1556-0864 Vol.17 N° 9 2022 págs. S433 - S434
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Autores: Puyalto Calvo, Ander; Rodríguez Remírez, María; López Erdozain, María Inés; et al.Revista: JOURNAL OF THORACIC ONCOLOGYISSN: 1556-0864 Vol.17 N° 9 2022 págs. S48 - S49
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Autores: Valencia, K.; Echepare, M.; Pasquier, A.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.82 N° 12 2022
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Autores: Sandua Condado, Amaia; Alegre Martínez, Estíbaliz; González Hernández, Álvaro (Autor de correspondencia)Revista: CANCERSISSN: 2072-6694 Vol.13 N° 17 2021 págs. 4330ResumenSimple Summary Lung cancer is a leading cause of cancer-related death worldwide and in most cases, detection is usually late and treatment resistance is frequent. For that reason, it is necessary to find biomarkers that could improve the diagnosis and disease management. Exosomes are a type of microvesicles secreted by tumor cells to the medium, with important functions in tumor development. Their analysis can be of utility in diagnosis, including early diagnosis, prognosis, treatment election or follow-up. However, isolation and analysis are cumbersome and can affect the subsequent data information. In this review, we will discuss the recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods. Lung cancer is a leading cause of cancer-related death worldwide and in most cases, diagnosis is reached when the tumor has already spread and prognosis is quite poor. For that reason, the research for new biomarkers that could improve early diagnosis and its management is essential. Exosomes are microvesicles actively secreted by cells, especially by tumor cells, hauling molecules that mimic molecules of the producing cells. There are multiple methods for exosome isolation and analysis, although not standardized, and cancer exosomes from biological fluids are especially difficult to study. Exosomes' cargo proteins, RNA, and DNA participate in the communication between cells, favoring lung cancer development by delivering signals for growth, metastasis, epithelial mesenchymal transition, angiogenesis, immunosuppression and even drug resistance. Exosome analysis can be useful as a type of liquid biopsy in the diagnosis, prognosis and follow-up of lung cancer. In this review, we will discuss recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.
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Autores: Narayanan, S.; Vicent Cambra, Silvestre (Autor de correspondencia); Ponz Sarvisé, Mariano (Autor de correspondencia)Título: PDAC as an immune evasive disease: can 3D model systems aid to tackle this clinical problem?Revista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGYISSN: 2296-634X Vol.9 2021 págs. 787249ResumenPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a high mortality rate. The presence of a dense desmoplastic stroma rich in fibroblasts, extracellular matrix, and immune cells plays a critical role in disease progression, therapy response and is a distinguishing feature of PDAC. PDAC is currently treated with a combination of surgery, chemotherapy and radiation therapy in selected cases which results in long-term survival only in a small percentage of patients. Cancer therapies that incorporate immunotherapy-based techniques have become increasingly common in recent years. While such a strategy has been shown to be effective for immunogenic, "hot" tumors like melanoma and lung cancer, thus far PDAC patients display poor responses to this therapeutic approach. Various factors, such as low tumor mutational burden, increased infiltration of immunosuppressive cells, like MDSCs and Treg cells promote tolerance and immune deviation, further aggravating adaptive immunity in PDAC. In this review we will elaborate on the ability of PDAC tumors to evade immune detection. We will also discuss various 3D model system that can be used as a platform in preclinical research to investigate rational combinations of immunotherapy with chemotherapy or targeted therapy, to prime the immune microenvironment to enhance antitumor activity.
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Autores: Adkins, D. R. (Autor de correspondencia); Lin, J. C.; Sacco, A.; et al.Revista: ORAL ONCOLOGYISSN: 1368-8375 Vol.115 2021 págs. 105192ResumenObjectives: This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab. Materials and methods: In this double-blind, randomized, phase 2 trial (PALATINUS), patients with platinumresistant, cetuximab-na?ve, human papillomavirus-unrelated recurrent/metastatic head and neck squamouscell carcinoma received cetuximab and either palbociclib (arm A) or placebo (arm B). The primary endpoint was OS; 120 patients were required to have ?80% power to detect a hazard ratio (HR) of 0.6 (median OS of 10 months in arm A and 6 months in arm B) using a one-sided, log-rank test (P = 0.10). Results: 125 patients were randomized (arm A: 65, arm B: 60). Median follow-up was 15.9 months (IQR, 11.3?22.7). Median OS was 9.7 months in arm A and 7.8 months in arm B (HR, 0.82; 95% CI, 0.54?1.25; P = 0.18). Median progression-free survival was 3.9 months in arm A and 4.6 months in arm B (HR, 1.00; 95% CI, 0.67?1.5; P = 0.50). The most common treatment-related adverse events in arm A were rash (39 patients, 60.9%) and neutropenia (26, 40.6%; three febrile) and in arm B was rash (32, 53.3%). Conclusion: There was no significant difference in median OS with palbociclib and cetuximab versus placebo and cetuximab. Funding: Pfizer Inc (NCT02499120).
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Autores: Macias Conde, Monica; García Cortés, Ángel; Torres Roca, Marcos; et al.Revista: CYTOKINEISSN: 1043-4666 Vol.141 2021 págs. 155471ResumenBackground: Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients. Methods: Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays. Results: All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patient¿ presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine ...
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Autores: Bockorny, B. ; Macarulla, T.; Semenisty, V.; et al.Revista: CLINICAL CANCER RESEARCHISSN: 1078-0432 Vol.27 N° 18 2021 págs. 5020 - 5027ResumenPurpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC. Patients and Methods: Multicenter, single-arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined with chemotherapy in patients with de novo metastatic PDAC and disease progression on front-line gemcitabine-based therapy (NCT02826486). Subjects received a priming phase of motixafortide daily on days 1-5, followed by repeated cycles of motixafortide twice a week; pembrolizumab every 3 weeks; and nanoliposomal irinotecan, fluorouracil, and leucovorin every 2 weeks (NAPOLI-1 regimen). The primary objective was objective response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), safety, and tolerability. Results: A total of 43 patients were enrolled. The ORR according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The DCR was 63.2% with median duration of clinical benefit of 5.7 months. In the intention-to-treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated, with toxicity comparable with the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection was 7%, lower than expected for this chemotherapy regimen. Conclusions: Triple combination of motixafortide, pembrolizumab, and chemotherapy was safe and well tolerated, and showed signs of efficacy in a population with poor prognosis and aggressive disease.
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Autores: Salas Benito, Diego; Conde Gallastegi, E.; Tamayo Uria, Ibon; et al.Revista: BRITISH JOURNAL OF CANCERISSN: 0007-0920 Vol.124 N° 6 2021 págs. 1138 - 1149ResumenBackground Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. Methods PD-1(-) and PD-1(+) CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. Results Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1(+) fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137(+) cells within the PD-1(+)CD8(+) TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. Conclusion We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1(+) TILs.
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Autores: Rodríguez Pérez, María; Ajona Martínez-Polo, Daniel; Seijo Maceiras, Luis Miguel; et al.Revista: TRANSLATIONAL LUNG CANCER RESEARCHISSN: 2218-6751 Vol.10 N° 2 2021 págs. 1165-1185ResumenLow dose computed tomography (LDCT) screening, together with the recent advances in targeted and immunotherapies, have shown to improve non-small cell lung cancer (NSCLC) survival. Furthermore, screening has increased the number of early stage-detected tumors, allowing for surgical resection and multimodality treatments when needed. The need for improved sensitivity and specificity of NSCLC screening has led to increased interest in combining clinical and radiological data with molecular data. The development of biomarkers is poised to refine inclusion criteria for LDCT screening programs. Biomarkers may also be useful to better characterize the risk of indeterminate nodules found in the course of screening or to refine prognosis and help in the management of screening detected tumors. The clinical implications of these biomarkers are still being investigated and whether or not biomarkers will be included in further decision-making algorithms in the context of screening and early lung cancer management still needs to be determined. However, it seems clear that there is much room for improvement even in early stage lung cancer disease-free survival (DFS) rates; thus, biomarkers may be the key to refine risk-stratification and treatment of these patients. Clinicians' capacity to register, integrate, and analyze all the available data in both high risk individuals and early stage NSCLC patients will lead to a better understanding of the disease's mechanisms, and will have a dire
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Autores: Ayala de la Pena, F. (Autor de correspondencia); Ortiz-Munoz, B.; Quintanar-Verduguez, T.; et al.Revista: CLINICAL AND TRANSLATIONAL ONCOLOGYISSN: 1699-048X Vol.23 N° 7 2021 págs. 1272 - 1280ResumenThe measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQC(ML)) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.
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Autores: Hidalgo, M.; Macarulla, T.; Semenisty, V. ; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
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Autores: Puyalto Calvo, Ander; Rodríguez Remírez, María; López, I.; et al.Revista: JOURNAL OF THORACIC ONCOLOGYISSN: 1556-0864 Vol.16 N° 10 2021 págs. S1007 - S1007
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Autores: Ponz Sarvisé, Mariano; Elez, E. ; Munoz, A.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
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Autores: Ponz Sarvisé, Mariano; de Carvajal, C.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.81 N° 13 Supl. S 2021
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Autores: Gil Bazo, Ignacio; Puyalto Calvo, Ander; Rodríguez Remírez, María; et al.Título: A novel 89Zr-anti-PD-1 immuno-PET-CT improves response assessment to immunotherapy in lung cancerRevista: ANNALS OF ONCOLOGYISSN: 0923-7534 Vol.32 N° Supl. 5 2021 págs. S1216 - S1217
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Autores: Narayanan, S.; Erice Azparren, Oihane; Feliu, I.; et al.Revista: CANCER RESEARCHISSN: 0008-5472 Vol.81 N° 22 2021 págs. 59 - 60
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Autores: Rolfo, C.; Cardona, A. F.; Cristofanilli, M.; et al.Revista: CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGYISSN: 1040-8428 Vol.151 2020 págs. 102978ResumenPrecision medicine was born with the development of new diagnostic techniques and targeted drugs, yielding better outcomes in cancer care. With the evolution and increasing sensitivity for detecting oncogenic drivers, liquid biopsies (LBs), specifically cell-free DNA (cfDNA) analysis, have been proposed as a minimally-invasive technique for genomic profiling. Ranging from sequencing techniques to PCR-based methods and other more complex strategies, this approach, currently applicable in some solid tumors with robust evidence, is showing promising opportunities in other cancers. However, difficulties in validating their clinical utility exist within limitation at different levels among several techniques, reporting of the results, lack of appropriate clinical trial designs, and unknown economic impact. One of the aims of the ISLB is to create recommendations to develop reliable and sustainable diagnostic, prognostic and predictive tools using LBs. This paper is addressing these objectives, helping the healthcare providers and scientific community to understand the potential of LB.
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Autores: Serrano, M. J. (Autor de correspondencia); Garrido-Navas, M. C.; Mochon, J. J. D.; et al.Revista: CANCER DISCOVERYISSN: 2159-8274 Vol.10 N° 11 2020 págs. 1635 - 1644ResumenDespite major therapeutic progress, most advanced solid tumors are still incurable. Cancer interception is the active way to combat cancer onset, and development of this approach within high-risk populations seems a logical first step. Until now, strategies for the identification of high-risk subjects have been based on low-sensitivity and low-specificity assays. However, new liquid biopsy assays, "the Rosetta Stone of the new biomedicine ere with the ability to identify circulating biomarkers with unprecedented sensitivity, promise to revolutionize cancer management. This review focuses on novel liquid biopsy approaches and the applications to cancer interception. Cancer interception involves the identification of biomarkers associated with developing cancer, and includes genetic and epigenetic alterations, as well as circulating tumor cells and circulating epithelial cells in individuals at risk, and the implementation of therapeutic strategies to prevent the beginning of cancer and to stop its development. Large prospective studies are needed to confirm the potential role of liquid biopsy for early detection of precancer lesions and tumors.
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Autores: Baraibar Argota, Iosune; Mezquita, L. ; Gil Bazo, Ignacio; et al.Revista: CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGYISSN: 1040-8428 Vol.148 2020 págs. 102906ResumenApproximately 4% of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) present EGFR exon 20 in-frame insertions, accounting for 0.3 %-3.7 % of NSCLC. In addition, 2 %-4 % of patients with NSCLC harbor human epidermal growth factor receptor 2 gene (HER2) mutations, being the 90 % of them exon 20 insertions. These mutations confer intrinsic resistance to available EGFR tyrosine kinase inhibitors (TKIs) and anti-HER2 treatments, as they result in steric hindrance of the drug-binding pocket. Therefore, no targeted therapies have been approved for NSCLC patients with EGFR or HER2 exon 20- activating mutations to date and remain an unmet clinical need. Promising efforts to novel treatment development have been made. Early data provide encouraging activity of novel drugs targeting EGFR and HER2 mutations in metastatic NSCLC. In this review we will summarize all the data reported to date about these driver molecular alterations and potential targeted therapies.
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Autores: Rolfo, C.; Cardona, A. F.; Cristofanilli, M. ; et al.Revista: CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGYISSN: 1040-8428 Vol.154 2020
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Autores: Gil Bazo, Ignacio (Autor de correspondencia)Revista: CANCERSISSN: 2072-6694 Vol.12 N° 11 2020 págs. 3373
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Autores: Eguren Santamaría, Iñaki; Fernández de Sanmamed Gutiérrez, Miguel; Gil Bazo, Ignacio (Autor de correspondencia)Revista: JOURNAL OF THORACIC ONCOLOGYISSN: 1556-0864 Vol.15 N° 4 2020 págs. 489 - 492
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Autores: Bockorny, B.; Semenisty, V. ; Macarulla, T.; et al.Revista: NATURE MEDICINEISSN: 1078-8956 Vol.26 N° 6 2020 págs. 878 ¿ 885ResumenResults from the phase IIa COMBAT trial combining CXCR4 and PD-1 inhibition in patients with metastatic cancer show encouraging clinical responses in association with enhanced antitumor immune activation. Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC (). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8(+) effector T cell tumor infiltration, decreased myeloid-derived suppressor cells (MDSCs) and further decreased circulating regulatory T cells. In cohort 2, 22 patients received BL-8040 and pembrolizumab with chemotherapy, with an ORR, DCR and median duration of response of 32%, 77% and 7.8 months, respectively. These data suggest that combined CXCR4 and PD-1 blockade may expand the benefit of chemotherapy in PDAC and warrants confirmation in subsequent randomized trials.
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Autores: Sendino, T.; Sandúa, A.; Calleja, S.; et al.Revista: ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIOISSN: 2628-491X Vol.1 N° 4 2020 págs. 1 - 5
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Autores: Macias Conde, Monica; Cañada Higueras, Eva María; Alegre Martínez, Estíbaliz; et al.Revista: CLINICAL CHEMISTRY AND LABORATORY MEDICINEISSN: 1434-6621 Vol.58 N° 8 2020 págs. 1341 - 1348ResumenBackground: Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Nextgeneration sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms. Here we compare two NGS panels for cfDNA: OncomineT Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360 (R) (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory. Methods: Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360 (R) (G360) was requested as part of their clinical assistance. Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with OncomineT Pan-Cancer (OM) panel in an Ion GeneStudio S5T System. Results: cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01). Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM. Conclusions: In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.
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Autores: Izaguirre Ascargorta, Maitane ; Fernández Landázuri, Sara; Mugueta Uriaque, María del Carmen; et al.Libro: Principios de Bioquímica Clínica y Patología MolecularISSN: 978-84-9113-389-6 Vol.3 2019 págs. 33-40
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Autores: Ramirez Ruiz, Maria Carla; González Hernández, Álvaro; Alegre Martínez, Estíbaliz; et al.Libro: Principios de bioquímica clínica y patología molecularISSN: 978-84-9113-386-6 2019 págs. 69 - 78
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Autores: Recalde Zamacona, Borja; Cano Rafart, David; Ezponda Casajús, Ana; et al.Título: NeumologíaLibro: Guía de Inmunotoxicidad. Diagnóstico y manejo de los efectos secundarios asociados a inmunoterapia en oncologíaISSN: 9788431333003 N° 8 2019 págs. 108-113
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Autores: Martínez Espartosa, Débora; González Hernández, Álvaro; Alegre Martínez, Estíbaliz; et al.Título: Elementos trazaLibro: Principios de Bioquímica Clínica y patología molecularISSN: 978-84-9113-389-6 Vol.3 2019 págs. 143-152
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Autores: Martínez Espartosa, Débora; Ramirez Ruiz, Maria Carla; González Hernández, Álvaro; et al.Título: Estudio bioquímico del embarazoLibro: Principios de bioquímica clínica y patología molecularISSN: 978-84-9113-389-6 Vol.3 2019 págs. 325-332
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Autores: Ramirez Ruiz, Maria Carla; González Hernández, Álvaro; Alegre Martínez, Estíbaliz; et al.Libro: Principios de bioquímica clínica y patología molecularISSN: 978-84-9113-386-6 2019 págs. 151 - 164
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Autores: Martínez Espartosa, Débora; González Hernández, Álvaro; Alegre Martínez, Estíbaliz; et al.Título: Hormonas sexualesLibro: Principios de Bioquímica Clínica y Patología MolecularISSN: 978-84-9113-389-6 Vol.3 2019 págs. 313-324
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Autores: Ponz Sarvisé, Mariano; de la Riva Onandía, Susana Rosa; Mora Moriana, LorenaTítulo: DigestivoLibro: Guia inmuno-toxicidad: diagnóstico y manejo de los efectos secundarios asociados a inmunoterapia en oncologíaISSN: 978-84-313-3300-3 2018 págs. 53 - 61
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Autores: Macias Conde, Monica; Alegre Martínez, Estíbaliz; Díaz-Lagares, A.; et al.Libro: Advances in Clinical ChemistryISSN: 978-0-12-815207-2 Vol.83 2018 págs. 73 - 119ResumenLiquid biopsy refers to the molecular analysis in biological fluids of nucleic acids, subcellular structures, especially exosomes, and, in the context of cancer, circulating tumor cells. In the last 10 years, there has been an intensive research in liquid biopsy to achieve a less invasive and more precise personalized medicine. Molecular assessment of these circulating biomarkers can complement or even surrogate tissue biopsy. Because of this research, liquid biopsy has been introduced in clinical practice, especially in oncology, prenatal screening, and transplantation. Here we review the biology, methodological approaches, and clinical applications of the main biomarkers involved in liquid biopsy.
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Autores: González Hernández, Álvaro (Editor)ISSN: 9788491133896 2019ResumenNueva edición de la obra en el campo de la bioquímica clínica que año tras año se está convirtiendo en una herramienta fundamental para la toma de decisiones del clínico, ya que gran parte de ellas se basan en los datos proporcionados por el laboratorio que necesitan por una interpretación adecuada teniendo en cuenta los diferentes factores preanalíticos y analíticos que puedan influir en ellos. Uno de las novedades más importantes de la bioquímica clínica es que ha ido incorporando progresivamente técnicas propias de la biología molecular y la proteómica.
Proyectos desde 2018
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Título: Desarrollo de un test para el diagnóstico precoz no invasivo de cáncer de pulmón basado en marcadores moleculares, imágenes y herramientas de Big Data-oncoLung DxCódigo de expediente: CPP2021-008336Investigador principal: LUIS MIGUEL SEIJO MACEIRAS.Financiador: AGENCIA ESTATAL DE INVESTIGACIONConvocatoria: 2021 AEI Proyectos en Colaboración Público PrivadaFecha de inicio: 01-06-2022Fecha fin: 31-05-2025Importe concedido: 174.754,00€Otros fondos: Fondos MRR
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Título: GRANATE - GRUPO DE RADIOTERAPIA AVANZADA DE NAVARRA ¿ TERAPIA Y EFICACIACódigo de expediente: 0011-1411-2022-000066Investigador principal: ANA PATIÑO GARCIA.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025Fecha de inicio: 01-06-2022Fecha fin: 31-12-2024Importe concedido: 536.739,00€Otros fondos: -
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Título: Nuevas opciones de imagen metabólica en la caracterización de la respuesta inducida por el bloqueo combinado de anti-PD-1 e Id1 y su correlación con la generación de neontígenos en un modelo de cáncer de pulmónCódigo de expediente: GNS_53-2021Investigador principal: IGNACIO GIL BAZO.Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUDConvocatoria: 2021 GN Proyectos de Investigación en saludFecha de inicio: 23-12-2021Fecha fin: 22-12-2024Importe concedido: 78.487,50€Otros fondos: -
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Título: Aplicaciones del estudio multi-ómico de la microbiota al desarrollo de soluciones biotecnológicas innovadoras en el área de la salud (microBiomics)Código de expediente: 0011-1411-2021-000106Investigador principal: MARIA TERESA HERRAIZ BAYOD, MARIA TERESA HERRAIZ BAYOD.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2021 GN PROYECTOS ESTRATEGICOS DE I+D 2021-2024Fecha de inicio: 15-04-2021Fecha fin: 30-11-2023Importe concedido: 366.577,17€Otros fondos: -
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Título: Estudios funcionales, moleculares y clínicos del papel de la lámina C2 (LAMC2) en el cáncer de páncreasCódigo de expediente: PI20/01718Investigador principal: MARIANO PONZ SARVISE, MARIANO PONZ SARVISE.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2020 AES Proyectos de investigaciónFecha de inicio: 01-01-2021Fecha fin: 31-12-2023Importe concedido: 85.910,00€Otros fondos: Fondos FEDER
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Título: platafoRma de intElIgeNcia artiFicial para la predicción de tOxicidad y Recurrencia del CancECódigo de expediente: 0011-1411-2020-000074Investigador principal: JAVIER RODRIGUEZ RODRIGUEZ, JAVIER RODRIGUEZ RODRIGUEZ, JAVIER RODRIGUEZ RODRIGUEZ.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2020 GN PROYECTOS ESTRATEGICOS DE I+D 2020-2022Fecha de inicio: 22-06-2020Fecha fin: 30-11-2022Importe concedido: 212.396,26€Otros fondos: -
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Título: Nuevas combinaciones inmunomoduladoras frente al adenocarcinoma de pulmón según el estado mutacional del oncogen KRAS. Estudio de nuevos biomarcadores de respuesta a terapia anti-PD-1Código de expediente: PI19/00678Investigador principal: IGNACIO GIL BAZO.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2019 AES Proyectos de investigaciónFecha de inicio: 01-01-2020Fecha fin: 31-12-2022Importe concedido: 111.320,00€Otros fondos: Fondos FEDER
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Título: Desarrollo EStratégico de terapias CART para el tratamiento de Tumores Hematológicos y Sólidos (DESCARTHeS)Código de expediente: 0011-1411-2019-000072Investigador principal: FELIPE LUIS PROSPER CARDOSO.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2019 GN PROYECTOS ESTRATEGICOS DE I+D 2019-2021Fecha de inicio: 01-04-2019Fecha fin: 30-11-2021Importe concedido: 164.695,50€Otros fondos: -
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Título: Nueva estrategia terapéutica para evitar el escape inmune en cáncer de pulmón metastásico mediante el bloqueo combinado de PD-1 e Id1Código de expediente: 74/2017Investigador principal: IGNACIO GIL BAZO, IGNACIO GIL BAZO.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2017 GN SALUDFecha de inicio: 01-01-2018Fecha fin: 15-12-2020Importe concedido: 90.000,00€Otros fondos: Fondos FEDER
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Título: Potenciación de la inmunoterapia frente al cáncer de pulmón mediante la modulación de la respuesta tumoral innataCódigo de expediente: PI17/00411Investigador principal: RUBEN PIO OSES, DANIEL AJONA MARTINEZ - POLO.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2017 - PROYECTOS DE I+D EN SALUDFecha de inicio: 01-01-2018Fecha fin: 31-12-2020Importe concedido: 123.420,00€Otros fondos: Fondos FEDER
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Título: Caracterización de la recíproca interacción oncogén/ remodeladores de cromatina en tumorogénesis y metástasis en el cáncer de pulmónCódigo de expediente: 77/2017Investigador principal: FERNANDO LECANDA CORDERO, FERNANDO LECANDA CORDERO.Financiador: GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUDConvocatoria: 2017 PROYECTOS DE I+D EN SALUDFecha de inicio: 15-12-2017Fecha fin: 15-09-2021Importe concedido: 64.842,75€Otros fondos: Fondos FEDER
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Título: Tecnología de secuenciación de nueva generación (NGS) para optimizar la eficacia del diagnóstico y tratamiento en pacientes con tumores de alta mortalidad (DIANA: Diagnostico biomédico e Innovación Abierta en Navarra)Código de expediente: 0011-1411-2017-000030Investigador principal: FELIPE LUIS PROSPER CARDOSO, FELIPE LUIS PROSPER CARDOSO.Financiador: GOBIERNO DE NAVARRAConvocatoria: 2017 GN ESTRATEGICOSFecha de inicio: 01-04-2017Fecha fin: 30-11-2019Importe concedido: 37.315,72€Otros fondos: -
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Título: Análisis molecular mediante plataformas de última generación del carcinoma no microcítico de pulmón para el desarrollo de perfiles pronósticos y nuevas herramientas terapéuticasCódigo de expediente: PI16/01821Investigador principal: LUIS MONTUENGA BADIA.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2016 - PROYECTOS DE I+D EN SALUDFecha de inicio: 01-01-2017Fecha fin: 31-12-2019Importe concedido: 128.865,00€Otros fondos: Fondos FEDER
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Título: Estudio pronóstico y predictivo de células tumorales circulantes (CTC) en adenocarcinoma de pulmón. Valoración invivo del papel de Id1 e Id3 en la capacidad metastásica de las CTCCódigo de expediente: PI15/02223Investigador principal: IGNACIO GIL BAZO, IGNACIO GIL BAZO.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2015 AES PROYECTOS DE INVESTIGACIÓNFecha de inicio: 01-01-2016Fecha fin: 30-11-2020Importe concedido: 92.565,00€Otros fondos: -
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Título: Estudio de coste-efectividad y factibilidad del cribado de cáncer de pulmón en EspañaCódigo de expediente: PI15/02157Investigador principal: JAVIER JOSEPH ZULUETA FRANCES, JAVIER JOSEPH ZULUETA FRANCES.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2015 AES PROYECTOS DE INVESTIGACIÓNFecha de inicio: 01-01-2016Fecha fin: 31-12-2018Importe concedido: 62.315,00€Otros fondos: -
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Título: Estudio de exosomas tumorales como inductores de células mieloides supresoras y mensajeros transportadores de moléculas inmunosupresoras.Código de expediente: PI14/00274Investigador principal: ALVARO GONZALEZ HERNANDEZ, ALVARO GONZALEZ HERNANDEZ.Financiador: INSTITUTO DE SALUD CARLOS IIIConvocatoria: 2014 ISCIII Proyectos de I+DFecha de inicio: 01-01-2015Fecha fin: 31-12-2018Importe concedido: 55.055,00€Otros fondos: -
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Título: PancREatic Cancer OrganoiDs rEsearch NetworkCódigo de expediente:Investigador principal: MARIANO PONZ SARVISE MARIANO PONZ SARVISEFinanciador: COMISIÓN EUROPEAConvocatoria: MSCA-ITN-2019 H2020Fecha de inicio: 01-10-2019Fecha fin: 30-09-2023Importe concedido: 250.904,88€Otros fondos: -
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Título: Rational gene signature-based drug combinations for lung cancer treatmentInvestigador principal: SILVESTRE VICENT CAMBRA, SILVESTRE VICENT CAMBRAFinanciador: ASOCIACION ESPAÑOLA CONTRA EL CANCERConvocatoria: FIMA 2020 Estratégicos AECCFecha de inicio: 01-11-2020Fecha fin: 31-10-2023Importe concedido: 300.000,00€
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Título: Determinación endotelinas ensayo clínico N-003-CRD003Investigador principal: ESTIBALIZ ALEGRE MARTINEZFecha de inicio: 04-07-2019Fecha fin: 15-06-2021Importe: 0Otros fondos: -
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Título: Determinaciones 50 actividades MAO-B en plaquetasInvestigador principal: ESTIBALIZ ALEGRE MARTINEZ, ESTIBALIZ ALEGRE MARTINEZFecha de inicio: 13-05-2019Fecha fin: 01-07-2019Importe: 0Otros fondos: -
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Título: Biomarcadores en sangre de pacientes con cáncer renalInvestigador principal: ALVARO GONZALEZ HERNANDEZFecha de inicio: 28-06-2018Fecha fin: 30-06-2020Importe: 0Otros fondos: -
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Título: Caracterización LAMC2 en Cáncer páncreasInvestigador principal: MARIANO PONZ SARVISEFecha de inicio: 12-06-2018Fecha fin: 12-06-2019Importe: 0Otros fondos: -
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Título: Nueva estrategia terapéutica para evitar el escape inmune en cáncer de pulmón metastásico mediante el bloqueo combinado PD-1 e Id1Investigador principal: IGNACIO GIL BAZO, IGNACIO GIL BAZOFinanciador: FUNDACION MERCK SALUDConvocatoria: 2016 MERCK SALUDFecha de inicio: 01-06-2017Fecha fin: 06-06-2020Importe concedido: 30.000,00€