2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.07 Ricciuti

PP01.07 Ricciuti - Abstract

Pdf Summary

KRAS amplification has been identified as a de novo oncogenic driver in non-small cell lung cancer (NSCLC). This study investigated the oncogenic potential of KRAS amplification and its association with unique subsets of NSCLCs. The research utilized clinicopathologic and genomic data from multiple cohorts, including whole transcriptome sequencing and proteomics analysis. Among the 15,341 NSCLC patients studied, KRAS amplification was found in 2.4% of cases, with distinct characteristics such as male gender, smoking history, and higher tumor mutational burden. KRAS amplification was associated with increased KRAS RNA and protein expression levels, as well as worse overall survival outcomes. Experimental models demonstrated that KRAS overexpression alone can drive cell proliferation, MAPK activation, tumor formation, and metastasis. The findings suggest that KRAS amplification defines a unique subset of oncogene-driven NSCLCs with poor survival outcomes, highlighting the importance of developing targeted therapeutic strategies for this specific group of NSCLC patients to improve treatment outcomes.

Keywords

KRAS amplification

non-small cell lung cancer

oncogenic driver

clinicopathologic data

genomic data

transcriptome sequencing

proteomics analysis

tumor mutational burden

cell proliferation

targeted therapeutic strategies