Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors.
10.1007/s11684-022-0951-0
- Author:
Shi-Yong SUN
1
Author Information
1. Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA. ssun@emory.edu.
- Publication Type:Review
- Keywords:
EGFR inhibitor;
acquired resistance;
apoptosis;
lung cancer
- MeSH:
Humans;
Drug Resistance, Neoplasm/genetics*;
Mutation;
Protein Kinase Inhibitors/therapeutic use*;
ErbB Receptors;
Lung Neoplasms/genetics*;
Apoptosis
- From:
Frontiers of Medicine
2022;16(5):701-713
- CountryChina
- Language:English
-
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.
