@misc{10481/71900,
year = {2021},
month = {10},
url = {http://hdl.handle.net/10481/71900},
abstract = {A shared characteristic of many tumors is the lack of response to anticancer drugs. Multiple mechanisms of
pharmacoresistance (MPRs) are involved in permitting cancer cells to overcome the effect of these agents.
Pharmacoresistance can be primary (intrinsic) or secondary (acquired), i.e., triggered or enhanced in response to
the treatment. Moreover, MPRs usually result in the lack of sensitivity to several agents, which accounts for
diverse multidrug-resistant (MDR) phenotypes. MPRs are based on the dynamic expression of more than one
hundred genes, constituting the so-called resistome. Alternative splicing (AS) during pre-mRNA maturation results
in changes affecting proteins involved in the resistome. The resulting splicing variants (SVs) reduce the
efficacy of anticancer drugs by lowering the intracellular levels of active agents, altering molecular targets,
enhancing both DNA repair ability and defensive mechanism of tumors, inducing changes in the balance between
pro-survival and pro-apoptosis signals, modifying interactions with the tumor microenvironment, and favoring
malignant phenotypic transitions. Reasons accounting for cancer-associated aberrant splicing include mutations
that create or disrupt splicing sites or splicing enhancers or silencers, abnormal expression of splicing factors, and
impaired signaling pathways affecting the activity of the splicing machinery. Here we have reviewed the impact
of AS on MPR in cancer cells.},
organization = {CIBERehd	EHD15PI05/2016},
organization = {Instituto de Salud Carlos III	PI16/00598	
PI19/00819},
organization = {European Regional Development Fund/European Social Fund, "Investing in your future"},
organization = {Spanish Ministry of Economy, Industry and Competitiveness	SAF201675197-R	
SAF2017-88457-R	
AGL2017-85270-R},
organization = {Junta de Castilla y Leon	SA063P17},
organization = {Junta de Andalucia	CTS235	
CTS164},
organization = {AECC Scientific Foundation, Spain},
organization = {University of Salamanca	18.K137/463AC01	
18. K140/463AC01},
organization = {"Centro Internacional sobre el Envejecimiento" (OLDHEPAMARKER), Spain	0348_CIE_6_E},
organization = {Fundacion University of Salamanca, Spain	PC-TCUE18-20_051},
organization = {Fundacio Marato TV3	201916-31},
organization = {Ministry of Science, Innovation and Universities, Spain},
publisher = {Elsevier},
keywords = {Alternative splicing},
keywords = {Chemoresistance},
keywords = {Chemotherapy},
keywords = {Pharmacoresistance},
keywords = {Tumor},
keywords = {Spliceosome},
title = {Impact of alternative splicing on mechanisms of resistance to anticancer drugs},
doi = {10.1016/j.bcp.2021.114810},
author = {Reviejo, María and Martínez Augustín, María Olga and Sánchez De Medina López-Huertas, Fermín},
}