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ПРЕОДОЛЕНИЕ РЕЗИСТЕНТНОСТИ КЛЕТОЧНЫХ ЛИНИЙ МЕЛАНОМЫ К ТАРГЕТНЫМ ИНГИБИТОРАМ B-RAF ЗА СЧЕТ ИНАКТИВАЦИИ РЕЦЕПТОРНЫХ ТИРОЗИНКИНАЗ, 'Молекулярная биология'
- Source :
- Молекулярная биология. :466-473
- Publication Year :
- 2018
- Publisher :
- Akademizdatcenter Nauka, 2018.
-
Abstract
- The discovery of B-RAF activating mutations in malignant melanoma cells has led to the development of a number of targeted drugs, which block exclusively the mutant B-RAF protein. Tumor cells often acquire resistance to B-RAF inhibitors via activation of alternative signaling pathways. One of the resistance mechanisms is activation of PDGF, VEGF, c-KIT, and certain other tyrosine kinases. The possibility of overcoming the resistance to the B-RAF inhibitor Vemurafenib by inactivating receptor tyrosine kinases (RTKs) was studied in metastatic melanoma cell lines differing in B-RAF mutations and RTK activity. It was found that RTK inactivation may help to overcome resistance to B-RAF inhibitors via inhibition of tyrosine kinase phosphorylation and a subsequent blocking of the PI3K-AKT-mTOR and MEK-ERK1/2 downstream signaling pathways. The changes eventually mitigated the cell growth and enhanced the Vemurafenib-dependent cell cycle arrest.
- Subjects :
- 0301 basic medicine
biology
Chemistry
Cell growth
Receptor Protein-Tyrosine Kinases
General Medicine
Receptor tyrosine kinase
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
030220 oncology & carcinogenesis
biology.protein
medicine
Cancer research
Phosphorylation
Signal transduction
Vemurafenib
Tyrosine kinase
Platelet-derived growth factor receptor
medicine.drug
Subjects
Details
- ISSN :
- 00268984
- Database :
- OpenAIRE
- Journal :
- Молекулярная биология
- Accession number :
- edsair.doi...........e103c4f433a6fc8433a6b64d3d49a1d2