Acquired Drug Resistance Mechanism of Osimertinib in the Targeted Therapy of Non-small Cell Lung Cancer.
10.3779/j.issn.1009-3419.2020.103.02
- Author:
Zitong ZHAO
1
;
Yu NI
1
;
Li LI
1
;
Tao XIN
1
Author Information
1. Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
- Publication Type:Journal Article
- Keywords:
EGFR;
EGFR-TKI;
Lung neoplasms;
Osimertinib;
T790M
- From:
Chinese Journal of Lung Cancer
2020;23(4):274-281
- CountryChina
- Language:Chinese
-
Abstract:
While treating cancer, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) still faces inevitable drug resistance. Investigations into the mechanisms which foster resistance to EGFR-TKI has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKI, and is a standard-of-care predictive biomarker used in therapeutic stratification. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR-TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR-TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and first-generation EGFR-TKI in randomized clinical trials. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR-TKIs, and envisions future directions in translational and clinical research.
