title: Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: VU University Medical Center, Department of Pediatric Oncology/Hematology , Amsterdam , The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Wojtuszkiewicz
authors.forename: Yehuda G
authors.initials: YG
authors.lastname: Assaraf
authors.forename: Marielle J P
authors.initials: MJ
authors.lastname: Maas
authors.forename: Gertjan J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: Gerrit
authors.initials: G
authors.lastname: Jansen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cloos
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012322:RNA Precursors / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D012322:RNA Precursors
keywords: cancer therapy; drug resistance; hematological malignancies; oligonucleotides; prognosis; spliceosome; splicing factors