RT Journal Article
T1 Impact of alternative splicing on mechanisms of resistance to anticancer drugs.
A1 Reviejo, Maria
A1 Soto, Meraris
A1 Lozano, Elisa
A1 Asensio, Maitane
A1 Martínez-Augustin, Olga
A1 Sánchez de Medina, Fermín
A1 Marin, Jose J G
K1 Alternative splicing
K1 Chemoresistance
K1 Chemotherapy
K1 Pharmacoresistance
K1 Spliceosome
K1 Tumor
AB 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.
YR 2021
FD 2021-10-19
LK https://hdl.handle.net/10668/25027
UL https://hdl.handle.net/10668/25027
LA en
DS RISalud
RD Apr 10, 2025