153 (PB033) - Using Tipifarnib to prevent resistance to targeted therapies in oncogene-addicted tumors

Abstract

Purpose: Targeted therapies can provide impressive responses in oncogene-addicted tumors, but are almost never curative due to the inevitable emergence of resistance. In this context, Drug-Tolerant Cells (DTC) have emerged as a new relevant concept which could explain the very first step of drug resistance, particularly in non-small cell lung cancers (NSCLC) and metastatic melanoma. We recently discovered that the farnesyltransferase inhibitor (FTi) tipifarnib can prevent the emergence of resistance to tyrosine kinase inhibitors in EGFR-mutant NSCLC in vitro and in vivo, by interfering with several key factors of the adaptive response, such as Rho GTPases and cell division-related proteins (Figarol et al., BioRxiv 2022).