[Inactivation of Receptor Tyrosine Kinases Overcomes Resistance to Targeted B-RAF Inhibitors in Melanoma Cell Lines].

Autor:	Ryabaya OO; Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia.; Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, 117997 Russia.; oxa2601@yandex.ru., Malysheva AA; Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia., Khochenkova YA; Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia., Solomko ES; Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia., Khochenkov DA; Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, 115478 Russia.
Jazyk:	ruština
Zdroj:	Molekuliarnaia biologiia [Mol Biol (Mosk)] 2018 May-Jun; Vol. 52 (3), pp. 466-473.
DOI:	10.7868/S0026898418030096
Abstrakt:	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.
Databáze:	MEDLINE
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