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MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer
- Source :
- Pharmaceuticals, Vol 14, Iss 130, p 130 (2021), Pharmaceuticals
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) are currently the most effective treatment for non-small cell lung cancer (NSCLC) patients, who carry primary EGFR mutations. However, the patients eventually develop drug resistance to EGFR-TKIs after approximately one year. In addition to the acquisition of the EGFR T790M mutation, the activation of alternative receptor-mediated signaling pathways is a common mechanism for conferring the insensitivity of EGFR-TKI in NSCLC. Upregulation of the Mer receptor tyrosine kinase (MERTK), which is a member of the Tyro3-Axl-MERTK (TAM) family, is associated with a poor prognosis of many cancers. The binding of specific ligands, such as Gas6 and PROS1, to MERTK activates phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) cascades, which are the signaling pathways shared by EGFR. Therefore, the inhibition of MERTK can be considered a new therapeutic strategy for overcoming the resistance of NSCLC to EGFR-targeted agents. Although several small molecules and monoclonal antibodies targeting the TAM family are being developed and have been described to enhance the chemosensitivity and converse the resistance of EGFR-TKI, few have specifically been developed as MERTK inhibitors. The further development and investigation of biomarkers which can accurately predict MERTK activity and the response to MERTK inhibitors and MERTK-specific drugs are vitally important for obtaining appropriate patient stratification and increased benefits in clinical applications.
- Subjects :
- 0301 basic medicine
EGFR-TKI resistance
MERTK
Pharmaceutical Science
lcsh:Medicine
lcsh:RS1-441
Review
Receptor tyrosine kinase
lcsh:Pharmacy and materia medica
03 medical and health sciences
0302 clinical medicine
Epidermal growth factor
Drug Discovery
Medicine
Protein kinase B
PI3K/AKT/mTOR pathway
non-small cell lung cancer
biology
business.industry
GAS6
lcsh:R
respiratory tract diseases
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Molecular Medicine
Signal transduction
business
Tyrosine kinase
Subjects
Details
- Language :
- English
- ISSN :
- 14248247
- Volume :
- 14
- Issue :
- 130
- Database :
- OpenAIRE
- Journal :
- Pharmaceuticals
- Accession number :
- edsair.doi.dedup.....4c7ae7d70988325f37be04565a7466d3