Genomic Mediators of Therapeutic Response in EGFR-Driven Lung Cancer

Speaker

• Giorgia Foggetti: Cancer Researcher at IRCCS Ospedale San Raffaele (OSR) – Vita-Salute San Raffaele University (UniSR), Milan, Italy

Abstract

Targeted therapies based on the presence of oncogenic driver alterations have improved the survival of cancer patients, however, the heterogeneity of responses and the emergence of drug resistance remain a critical challenge. Thanks to a combination of in vivo modeling and CRISPR/Cas9-mediated somatic genome editing we are now able to interrogate the functional importance of tumor suppressor pathways in oncogene-driven human tumors.
Our recent work established a direct causal link between Keap1 and differential response to targeted therapy in a mouse model of EGFR-driven lung cancer. Our findings were further supported by correlative human mutational datasets thus reflecting treatment outcomes in the human disease. Dissecting the role of the KEAP1 pathway in EGFR-driven lung tumors could reveal therapeutic vulnerabilities leading to the development of genotype-specific therapeutic strategies.
More broadly, understanding how the interplay between oncogenic drivers and tumor suppressors may influence drug sensitivity will help in the identification of subgroups of patients who do not benefit from therapy and optimize treatment regimens.