BRAF/MEK inhibition in NSCLC: mechanisms of resistance and how to overcome it
Clin. transl. oncol. (Print)
; 25(1): 10-20, ene. 2023.
Article
in English
| IBECS
| ID: ibc-215818
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
Targeted therapy for oncogenic genetic alterations has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC). Mutations in the BRAF gene are detected in approximately 4% of patients and result in hyper-activation of the MAPK pathway, leading to uncontrolled cellular proliferation. Inhibition of BRAF and its downstream effector MEK constitutes a therapeutic strategy for a subset of patients with NSCLC and is associated with clinical benefit. Unfortunately, the majority of patients will develop disease progression within 1 year. Preclinical and clinical evidence suggests that resistance mechanisms involve the restoration of MAPK signaling which becomes inhibition-independent due to upstream or downstream alterations, and the activation of bypass pathways, such as the PI3/AKT/mTOR pathway. Future research should be directed to deciphering the mechanisms of cancer cells oncogenic dependence, understanding the tissue-specific mechanisms of BRAF-mutant tumors, and optimizing treatment strategies after progression on BRAF and MEK inhibition (AU)
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Collection:
National databases
/
Spain
Database:
IBECS
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Protein Kinase Inhibitors
/
Lung Neoplasms
Limits:
Humans
Language:
English
Journal:
Clin. transl. oncol. (Print)
Year:
2023
Document type:
Article
Institution/Affiliation country:
National and Kapodistrian University of Athens/Greece