Novel combination therapy of osimertinib and Tupichinol E in triple-negative breast cancer: Targeting EGFR and CDK4/6 pathways

Abstract

Triple-Negative Breast Cancer (TNBC) is one of the most challenging form of breast cancer that lacks hormone receptors and HER2, limiting targeted treatment options. While a third-generation EGFR inhibitor, Osimertinib, has shown efficacy in various cancers, its role in TNBC is not well established. On the other hand, Tupichinol E, a novel compound, has shown promising anticancer potential in preclinical studies. This study investigates the combined effects of Osimertinib and Tupichinol E on TNBC cell lines, revealing a synergistic reduction in cell viability, increased apoptosis, and cell cycle arrest compared to individual treatments. Furthermore, cyclindependent kinases 4 and 6 (CDK4/6), important cell cycle regulators, are essential in transitioning cells from the G1 to S phase via retinoblastoma protein (RB) phosphorylation. Dysregulation of the CDK4/6-RB pathway is a hallmark in many cancers, including hormone receptor-positive breast cancers, and has become a focus of targeted therapies. Our findings not only emphasizes the therapeutic potential of combining Osimertinib with Tupichinol E in TNBC but also underscore the importance of CDK4/6 inhibitors in modulating cell cycle progression, offering a promising avenue for combination therapies in TNBC treatment.