Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance.

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Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance.

Expert Opin Drug Metab Toxicol. 2015 May;11(5):673-89

Authors: Wojtuszkiewicz A, Assaraf YG, Maas MJ, Kaspers GJ, Jansen G, Cloos J

Abstract
INTRODUCTION: Aberrant pre-mRNA splicing in cancer is emerging as an important determinant of oncogenesis, response to treatment and anticancer drug resistance. At the same time, the spliceosome has become a target for a novel class of pre-clinical chemotherapeutics with a potential future application in cancer treatment. Taken together, these findings offer novel opportunities for the enhancement of the efficacy of cancer therapy.
AREAS COVERED: This review presents a comprehensive overview of the molecular mechanisms involved in splicing and current developments regarding splicing aberrations in relation to several aspects of cancer formation and therapy. Identified mutations in the various components of the spliceosome and their implications for cancer prognosis are delineated. Moreover, the contribution of abnormal splicing patterns as well as deregulated splicing factors to chemoresistance is discussed, along with novel splicing-based therapeutic approaches.
EXPERT OPINION: Significant progress has been made in deciphering the role of splicing factors in cancer including carcinogenesis and drug resistance. Splicing-based prognostic tools as well as therapeutic options hold great potential towards improvements in cancer therapy. However, gaining more in-depth molecular insight into the consequences of mutations in various components of the splicing machinery as well as of cellular effects of spliceosome inhibition is a prerequisite to establish the role of splicing in tumor progression and treatment options, respectively.

PMID: 25495223 [PubMed - indexed for MEDLINE]

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