Afatinib in KRAS driven Lung Adenocarcinoma

Despite of the enormous efforts of the scientific community unfortunately lung cancer is still the leading cause of cancer deaths worldwide. EGFR and KRAS are two oncogenes which are mutated in approximately 50% of lung tumors. While tumors harboring EGFR mutations respond well to EGFR inhibitors, the effect of EGFR inhibition in mutated KRAS lung tumors is not so clear. Within this proposal, we will validate afatinib (an EGFR inhibitor) combined with immune checkpoint blockers as an option for therapeutic treatment of KRAS-mutated Non-Small-Lung-Cancer. The final aim of this study will be to develop new therapeutic options to treat KRAS-mutated lung cancer.

Despite extensive research efforts, lung cancer remains the leading cause of cancer-related deaths globally. About one-third of lung cancer patients have a genetic mutation in the KRAS oncogene, which is associated with a poor prognosis and limited treatment options. Our previous studies have demonstrated that afatinib, an inhibitor targeting the ErbB receptor family, shows efficacy in experimental models of KRAS-mutated lung cancer. In our current research, we investigated whether afatinib's effectiveness might be partly due to its interaction with the immune system. We observed that afatinib treatment led to tumor regression in these models and, notably, increased the infiltration of tumors by immune cells that attack cancer. This indicates that afatinib not only induces cancer cell death but also enhances the immune system's ability to recognize and combat the tumor. These findings suggest that afatinib could be used in combination with immunotherapy, potentially expanding treatment options for patients with KRAS-mutated lung cancer and offering new avenues for combating this challenging disease.