2021 LCRF-AstraZeneca Research Grant
Giorgia Foggetti, PhD
Università Vita-Salute San Raffaele
Dissecting the Role of the KEAP1 Pathway in Mediating Therapeutic Sensitivity in EGFR-Driven Lung Adenocarcinoma
Lung cancer is the second most common cancer type worldwide and remains an uncurable disease. EGFR is a frequent biomarker of lung cancer and is found mutated in ~15% of all cases. The presence of EGFR mutations predicts the response to specific therapies referred to as tyrosine kinase inhibitors (TKIs). The 3rd generation TKI osimertinib is the standard of care for patients with this disease and improves the survival of patients. However, this therapy does not work in all patients with the same efficacy, and for many patients osimertinib will eventually stop working, highlighting the need for alternative treatment options.
KEAP1 is a gene involved in regulating oxidative stress and detoxification processes. In EGFR mutant tumors, mutations in the pathway of KEAP1 are associated with a poorer response to TKIs and therefore worse outcomes in patients. This project aims to investigate how inactivation of KEAP1 limits the response to therapy of EGFR mutant tumors to identify specific vulnerabilities for this subset of tumors. By testing novel therapeutic agents that target these vulnerabilities, these studies will help develop new strategies in combination with osimertinib to improve the response to treatment in patients affected by EGFR mutant lung cancer and evidence of dysregulation of the KEAP1 pathway.