KRAS driven lung adenocarcinoma depends on ERBB signaling
Ponente: Emilio Casanova-Hevia
Ludwig Boltzmann Institute Cancer Research [Vienna, Austria]
Host: Carmen Guerrero
Salón de actos del Centro de Investigación del Cáncer
Several clinical trials using first generation EGFR Tyrosine Kinase Inhibitors (TKIs, erlotinib and gefitinib) in patients suffering of lung adenocarcinoma (AC) harboring activating mutations in the KRAS gene have shown disappointing results. Therefore, it has become a dogma that KRAS driven lung AC do not respond to TKIs and targeting EGFR is not considered a therapeutic option to treat patients suffering of KRAS mutated lung AC. In agreement we that, we have shown that erlotinib and gefitinib are infective in KRAS driven lung AC. However, EGFR inhibition with erlotinib or gefitinib results in a tumor-escape mechanism depending on the (re)activation of non-EGFR ERBB receptors that explains the poor results in previous clinical trials using erlotinib and gefitinib. Consequently, afatinib, a pan-ERBB inhibitor, effectively abrogates KRAS driven lung AC. Thus, afatinib or other pan-ERBB inhibitors should be a therapeutic option to treat patients suffering of KRAS driven lung AC.