Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

Acta Pharm Sin B. 2023 Mar;13(3):982-997. doi: 10.1016/j.apsb.2022.10.002. Epub 2022 Oct 7.

Abstract

Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.

Keywords: ABC transporter family; Alternative splicing (AS); Gene mutation; Multidrug resistance (MDR); None-coding RNA (ncRNA); Signaling pathway; Tumor microenvironment.

Publication types

  • Review