EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: From molecular mechanisms to clinical research. (May 2021)

• Record Type: Journal Article
• Authors: Dong, Rui-Fang; Zhu, Miao-Lin; Liu, Ming-Ming; Xu, Yi-Ting; Yuan, Liu-Liu; Bian, Jing; Xia, Yuan-Zheng; Kong, Ling-Yi
• Is Part Of: Pharmacological research. Volume 167(2021)
• Publication Date: 2021-05
• Subjects: AACR American Association for Cancer Research -- ACTA2 α-smooth muscle actin -- ADCs antibody-drug conjugates -- AKT protein kinase B -- ASCO American Society of Clinical Oncology -- AUTAC autophagy-targeting chimera -- BCL2 B-cell lymphoma-2/lymphoma-2 -- Bcl-XL BCL2-like 1 -- BIM BCL2 interacting mediator of cell death -- BTD breakthrough therapy designation -- CDX cell-line-derived xenograft -- CNS central nervous system -- DCR disease control rate -- DOR duration of remission -- EGFR epidermal growth factor receptor -- EGFR-TKIs EGFR-tyrosine kinase inhibitors -- GRP78 glucose regulated protein 78 -- HER2 human epidermal receptor 2 -- LYTACs lysosome-targeting chimaeras -- MET hepatocyte growth factor receptor -- NSCLC non-small-cell lung cancer -- NOX nicotinamide adenine dinucleotide phosphate oxidase -- OS overall survival -- ORR objective response rate -- PD-1 programmed cell death protein 1, PD-L1, programmed death-ligand-1 -- PROTAC proteolysis targeting chimera -- PFS progression-free survival -- PDX patient-derived tumour xenograft -- PLC-PKC phospholipase C-protein kinase C -- PGAM1 phosphoglycerate mutase 1 -- RAF rapidly accelerated fibrosarcoma -- RAS rat sarcoma -- RTKs receptor tyrosine kinases -- STAT signal transducer and activator of transcription -- TPX2 targeting protein for Xklp2 -- TM transmembrane domain -- WCLC World Conference on lung cancer; TAK-788 (PubChem CID: 118607832) -- Poziotinib (PubChem CID: 25127713) -- TAS6417 (PubChem CID: 117918742) -- Osimertinib (PubChem CID: 71496458) -- Almonertinib (PubChem CID: 121280087) -- Alflutinib (PubChem CID: 118861389) -- TQB3804 (PubChem CID: 138911391) -- EAI045 (PubChem CID: 121231412) -- JBJ-04-125-02 (PubChem CID: 124173751) -- JND3229 (PubChem CID: 137628688); EGFR mutations -- NSCLC -- EGFR-TKI resistance -- Overcoming drug resistance -- Future development; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105583
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: With the development of precision medicine, molecular targeted therapy has been widely used in the field of cancer, especially in non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a well-recognized and effective target for NSCLC therapies, targeted EGFR therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) has achieved ideal clinical efficacy in recent years. Unfortunately, resistance to EGFR-TKIs inevitably occurs due to various mechanisms after a period of therapy. EGFR mutations, such as T790M and C797S, are the most common mechanism of EGFR-TKI resistance. Here, we discuss the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, highlight the development of targeted drugs to overcome EGFR mutation-mediated resistance, and predict the promising directions for development of novel candidates. Graphical Abstract: This review summarizes the mechanisms of EGFR mutation-based resistance and evolution. Update the clinical progress and promising directions for novel drug development of overcoming EGFR TKIs resistance. ga1