Revistas
Revista:
JOURNAL OF THORACIC ONCOLOGY
ISSN 1556-0864
Vol. 16
N° 10 Supl. S
Año 2021
Págs.S1007 - S1008
Autores:
Verdaguer, H.; Guardiola Fernandez, M.; Mancuso, F. M.; et al.
Revista:
JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X
Vol. 38
N° 15
Año 2020
Revista:
CANCERS
ISSN 2072-6694
Vol. 12
N° 11
Año 2020
Págs.31-69
Revista:
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
ISSN 1040-8428
Vol. 148
Año 2020
Págs.102906
Approximately 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.
Autores:
Martini, G.; Mancuso, F.M.; Elez, E.; et al.
Revista:
JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X
Vol. 38
N° 15
Año 2020
Revista:
JOURNAL OF THORACIC ONCOLOGY
ISSN 1556-0864
Vol. 14
N° 10
Año 2019
Págs.S320 - S320
Revista:
CANCER RESEARCH
ISSN 0008-5472
Vol. 79
N° 3
Año 2019
Págs.625 - 638
Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of inhibitor of differentiation-1 (Id1) in mutant KRAS LUAD. Analysis of LUAD cohorts from TCGA and SPORE showed that high expression of Id1 was a marker of poor survival in patients harboring mutant, but not wild-type KRAS. Abrogation of Id1 induced G(2)-M arrest and apoptosis in mutant KRAS LUAD cells. In vivo, loss of Id1 strongly impaired tumor growth and maintenance as well as liver metastasis, resulting in improved survival. Mechanistically, Id1 was regulated by the KRAS oncogene through JNK, and loss of Id1 resulted in down-regulation of elements of the mitotic machinery via inhibition of the transcription factor FOSL1 and of several kinases within the KRAS signaling network. Our study provides clinical, functional, and mechanistic evidence underscoring Id1 as a critical gene in mutant KRAS LUAD and warrants further studies of Id1 as a therapeutic target in patients with LUAD.
Significance: These findings highlight the prognostic significance of the transcriptional regulator Id1 in KRAS-mutant lung adenocarcinoma and provide mechanistic insight into how it controls tumor growth and metastasis.
Revista:
PLOS ONE
ISSN 1932-6203
Vol. 14
N° 5
Año 2019
Págs.e0215970
Background Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharma-codynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients. Methods Patients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks. Results A low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage >= 3 and linitis plastica absence, were correlated to a higher risk of death. Conclusion Our model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.
Revista:
DRUG SAFETY
ISSN 0114-5916
Vol. 42
N° 2
Año 2019
Págs.281 - 294
Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatment-related. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 29
N° Supl. 8
Año 2018
Págs.711
Background: In the era of big data, the presence of cancer in social media is undeniable. Twitter is one of the biggest networks worldwide, therefore, it establishes an enormous real-world data field of interest when studying health issues. As far as we know, there are no exploratory studies about the content or the authorship of tweets related to breast cancer.
Methods: Tweets (original and re-tweets) with the hashtag #BreastCancer posted on Twitter during a 7-day period were collected. For the analysis, tweets were categorised based on their content (medical vs non medical and if medical, appropriate vs inappropriate), user information (private account vs institution or public account), the aim of the tweet (patients¿ experience, relatives¿ experience, advertising, scientific content, fund-raising and patient advocacy) and also on the extent to which they indicated a stigmatising attitude towards cancer. Tweets were further grouped into subthemes: diagnosis, treatment, prognosis and prevention (life-style and other risk factors).
Results: A total of 6341 tweets were collected (3703 original and 2638 re-tweets). When analysing original tweets, only 31% had medical content and in these, 90% were considered to have appropriate content. A stigmatising attitude towards cancer was identified in 14.8% of the tweets classified as non-medical content. 60% of the tweets came from private accounts and 40% from institutions or public accounts. Most of the tweets came from patients¿ experiences (30.7%), followed by patient advocacy (25.3%). When considering subthemes, the most common topic was cancer prevention (44.5%). Description of tweets (%) containing #BreastCancer in a 7-day period.
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 29
N° Supl. 6
Año 2018
Págs.21 - 22
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 29
N° Supl. 9
Año 2018
Revista:
MOLECULAR CANCER
ISSN 1476-4598
Vol. 17
Año 2018
Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.
Revista:
JOURNAL OF THORACIC ONCOLOGY
ISSN 1556-0864
Vol. 13
N° 10
Año 2018
Págs.S375 - S376
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 29
N° Supl. 8
Año 2018
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 28
N° Supl 5
Año 2017
Págs.34P
Revista:
CANCER RESEARCH
ISSN 0008-5472
Vol. 77
N° 4 Supl.
Año 2017
Págs.P2-04-01
Revista:
JOURNAL OF THORACIC ONCOLOGY
ISSN 1556-0864
Vol. 12
N° 11 Supl. 2
Año 2017
Págs.S2008
Revista:
CANCER LETTERS
ISSN 0304-3835
Vol. 402
Año 2017
Págs.43 - 51
Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor nodules from Id1(+/+) mice and Idl(-/-) mice injected with LLC control cells revealed that Id1 loss reduces the levels of EMT-related proteins, such as vimentin. In tissue microarrays containing 532 NSCLC patients' samples, we found that Idl significantly correlated with vimentin and other EMT-related proteins. Idl loss decreased the levels of vimentin, integrin beta 1, TGF beta 1 and snail, both in vitro and in vivo. Therefore, Id1 enables both LLC and the host microenvironment for an effective liver colonization, and may represent a novel therapeutic target to avoid NSCLC liver metastasis. (C) 2017 Elsevier B.V. All rights reserved.
Revista:
CANCER RESEARCH
ISSN 0008-5472
Vol. 77
N° Supl. 4
Año 2017
Págs.P6-07-32
Revista:
ANNALS OF ONCOLOGY
ISSN 0923-7534
Vol. 27
N° Supl. 6
Año 2016
Págs.1270P
Revista:
REVISTA DE LA FUNDACION EDUCACION MEDICA
ISSN 2014-9832
Vol. 18
N° 1
Año 2015
Págs.35 - 38
Objetivo.
Conocer la valoración de los estudiantes respecto a la simulación como herramienta de formación y la opinión
sobre la figura del alumno instructor.
Sujetos y métodos.
El taller se realizó en el Centro de Simulación y tuvo una duración aproximada de 90 minutos. En cada
sesión estaba el alumno instructor con diez compañeros. Los alumnos instructores fueron formados previamente por un
profesor de cardiología. Al finalizar la sesión, los estudiantes cumplimentaron un cuestionario de satisfacción anónimo
que contenía preguntas relacionadas con el aprendizaje basado en la simulación y sobre la capacidad de sus compañeros
para actuar como formadores.
Resultados.
Se obtuvieron encuestas de 291 estudiantes: 150 de quinto y 141 de sexto curso (82,4% y 71,2% de los matri
-
culados, respectivamente). Los datos obtenidos del cuestionario de satisfacción respecto a la metodología de aprendizaje
obtuvieron puntuaciones entre 3,64 y 4,75 sobre 5. Las preguntas que valoraban la opinión acerca de los alumnos forma
-
dores obtuvieron valores entre 4,88 y 4,93 sobre 5.
Conclusiones.
La simulación es una herramienta docente complementaria muy valiosa. La participación de alumnos ins
-
tructores podría ser una ayuda adicional en los talleres de simulación de exploración cardiológica.
