Role of KRAS mutation on NSCLC resistance to X-rays and protons

Juliette Montanari (1) , Mathieu Césaire (1) , Antoine Gilbert (1) , François Chevalier (1)

1 ARIA - Accueil et Recherche en Radiobiologie des Ions Accélérés

Unresectable locally advanced non-small cell lung cancer (NSCLC) is a frequent cancer with a prognosis that remains poor despite several treatments for radiotherapy, chemotherapy and immunotherapy. Mechanisms of resistance to treatments have been highlighted such as KRAS mutations. A new therapy type tyrosine kinase inhibitor targeting the KRAS G12C mutation has enabled efficacy in metastatic NSCLC and could have an interest in the treatment by radiotherapy locally advanced forms. However, the radiosensitizing effect of such molecules targeting KRAS remains unknown. KRAS resistance mechanisms could be related to hypoxia and the proliferation of tumor stem cells and irradiation by carbon ions and protons compared to photon irradiation might also have future interest in the treatment of these patients. In this study, we propose to use in vitro models of KRAS G12C mutated cell lines (vs. non-mutated). These cells are treated with a combination of KRAS G12C inhibitors and irradiations (X-rays, carbon ions and protons). Following a complete characterization of the cell lines and drug toxicity tests, the clonogenic survival of the cells is then analysed. Our preliminary results show a differential response of the cells, depending on the cell lines, irradiation doses and quality and drug combinations.

Domaines: Cancer; Biologie cellulaire; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Biochimie, Biologie Moléculaire; Biophysique [physics.bio-ph]

Juliette Montanari, Mathieu Césaire, Antoine Gilbert, François Chevalier. Role of KRAS mutation on NSCLC resistance to X-rays and protons. ERRS 2022 - 47th Annual Meeting of the European Radiation Research Society, Sep 2022, Catania, Italy. . ⟨hal-03808183⟩