2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.15 Lu

PP01.15 Lu - Poster

Pdf Summary

The document discusses the diversity of BRAF mutations in Non-Small Cell Lung Cancer (NSCLC) and its implications for treatment. BRAF mutations are observed in 5% of NSCLC cases, with three classes identified: Class I (active monomers), Class II (active dimers), and Class III (kinase dead domain). While combination anti-BRAF and anti-MEK inhibitors are FDA-approved for BRAF V600E-mutant NSCLC, there are currently no FDA-approved targeted therapies for Class II and Class III BRAF mutations. The study utilizes clinical data, computational modeling, and chemical drug screenings to assess the therapeutic implications of different BRAF variants. Results show that anti-BRAF/anti-MEK therapy is associated with improved overall survival in Class I BRAF mutations, while some Class III mutants may be resistant to BRAF inhibitors due to steric hindrance. In vitro testing demonstrated cell death in selected EGFR inhibitor in Class II and III cell lines. Further analysis is suggested to evaluate the clinical value of EGFR, ERK, MEK, and pan-RAF inhibition in Class II and III patients. The study includes references, survival analysis, in silico modeling of BRAF class III mutations, pharmacologic inhibition of Class II and III NSCLC cell lines, and demographic and genetic alteration data from a patient cohort.

Keywords

BRAF mutations

Non-Small Cell Lung Cancer

NSCLC

treatment implications

anti-BRAF inhibitors

anti-MEK inhibitors

therapeutic implications

clinical data

chemical drug screenings

EGFR inhibitor