Molecular mechanisms of drug resistance of glioblastoma part 1: ABC family proteins and inhibitors

Abstract

The most common high-grade brain tumor in the adult population is glioblastoma. The life expectancy of patients with this tumor does not exceed 12-15 months, while relapses are observed in 100% of cases. One of the main reasons for the low efficiency of glioblastoma therapy is its multidrug resistance. In the development of the latter, transporter proteins of the ABC family play a key role. In this part, the emphasis is on the search for new molecular targets among growth factors, their receptors, signal transduction kinases, microRNAs, transcription factors, protooncogenes, and tumor suppressor genes involved in the regulation of proteins and genes of the ABC family and associated with the development of multidrug resistance in glioblastoma cells. The review also discusses the mechanisms of the cytotoxic action of inhibitors: ABC family proteins, tyrosine kinase receptors, non-receptor tyrosine kinases, vascular endothelial growth factor, kinases of signaling cascades, transcription factors, histone deacetylases, methyltransferases, replication and synthesis of DNA, microtubules and proteasome used in glioblastoma therapy or undergoing clinical trials.

Keywords

glioblastoma / multidrug resistance / chemotherapy drugs / inhibitors / ABC-family transporter proteins / growth factors and receptors / signal transduction kinases / microRNA / transcription factors

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Chernov A.N., Shamova O.V.