AUTHOR=Tubita Alessandro , Fancelli Sara , Anela Lorenzo , Petroni Giulia , Caliman Enrico , Mazzoni Francesca , Scolari Federico , Napolitano Brunella , Menicacci Beatrice , Comin Camilla Eva , Voltolini Luca , Pillozzi Serena , Antonuzzo Lorenzo 

TITLE=KRAS G12C inhibition enhances efficacy to conventional chemotherapy in KRAS-mutant NSCLC

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1654491

DOI=10.3389/fonc.2025.1654491

ISSN=2234-943X

ABSTRACT=Despite recent therapeutic advances, the adjuvant treatment of non-small cell lung cancer (NSCLC) remains a challenge. Reducing the risk of recurrence is still a concern, especially in the KRAS G12C population, for which platinum-based adjuvant chemotherapy (CT) remains the gold standard. In this study, we evaluated the efficacy, in terms of cell viability and volumetric reduction, of adding KRAS inhibitors (KRASi) sequentially or concurrently to CT in both parental (PR) and gemcitabine-resistant (GR) KRAS mutated NSCLC cell lines (SW1573 and H23). We demonstrated that KRASi added to CT (both sequential and concurrent treatment strategies) reduced cell viability in SW1573-PR and H23-PR and this effect is less evident in GR cell lines. Interestingly, in the 3D model, the concomitant use of KRASi+CT reduced spheroid volume in both PR and GR spheroids. Our results indicate that KRASi enhances the efficacy of CT in both NSCLC PR and GR cells, suggesting a potential therapeutic strategy to overcome chemoresistance in the adjuvant setting of NSCLC.