Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

Abstract

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.

Keywords

acquired resistance / EGFR inhibitor / apoptosis / lung cancer

参考文献

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Acknowledgements

I am thankful to Dr. Anthea Hammond in my department for editing the manuscript. Some of work done in my laboratory were supported by the NIH/NCI R01 CA223220, R01 CA245386, UG1 CA233259 awards and Emory University Winship Cancer Institute lung cancer pilot funds. Shi-Yong Sun is a Georgia Research Alliance Distinguished Cancer Scientist.

Compliance with ethics guidelines

Shi-Yong Sun declares no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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