摘要
A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(EGFR-TKIs),such as osimertinib,which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations,in order to achieve maximal response duration or treatment remission.Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment.Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy.It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs,particularly osimertinib,to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance.Hence,restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.
基金
Some of work done in my laboratory were supported by the NIH/NCI R01 CA223220,R01 CA245386,UG1CA233259 awards and Emory University Winship Cancer Institute lung cancer pilot funds.