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Updated: Oct 16, 2025

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

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Impact of alternative splicing on mechanisms of resistance to anticancer drugs

Maria Reviejo1, Meraris Soto2, Elisa Lozano1

  • 1Experimental Hepatology and Drug Targeting (HEVEPHARM), University of Salamanca, Institute for Biomedical Research of Salamanca (IBSAL), Salamanca 37007, Spain; Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, Madrid 28029, Spain.

Biochemical Pharmacology
|October 21, 2021
PubMed

Insights

Alternative splicing (AS) generates splicing variants (SVs) that contribute to multiple mechanisms of pharmacoresistance (MPRs) in cancer. These variants impact drug efficacy by altering drug levels, targets, and cellular defense mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Many tumors exhibit resistance to anticancer drugs, a phenomenon known as pharmacoresistance.
  • Multiple mechanisms of pharmacoresistance (MPRs) enable cancer cells to evade drug effects, leading to treatment failure.
  • Pharmacoresistance can be intrinsic or acquired, often resulting in multidrug-resistant (MDR) phenotypes.

Purpose of the Study:

  • To review the impact of alternative splicing (AS) on multiple mechanisms of pharmacoresistance (MPRs) in cancer cells.
  • To elucidate how splicing variants (SVs) contribute to cancer drug resistance.
  • To explore the molecular underpinnings of AS-driven pharmacoresistance.

Main Methods:

  • Literature review focusing on alternative splicing and cancer pharmacoresistance.
  • Analysis of molecular mechanisms by which splicing variants affect drug response.
  • Synthesis of information on genetic and signaling pathways influencing aberrant splicing in cancer.

Main Results:

  • Alternative splicing (AS) generates diverse splicing variants (SVs) that are integral to the cancer resistome.
  • SVs reduce anticancer drug efficacy by altering intracellular drug levels, modifying drug targets, and enhancing cellular defense mechanisms.
  • Aberrant splicing in cancer is driven by mutations, altered splicing factor expression, and dysregulated signaling pathways.

Conclusions:

  • Alternative splicing plays a significant role in mediating multiple mechanisms of pharmacoresistance in cancer.
  • Splicing variants contribute to treatment failure by promoting drug resistance and enabling malignant progression.
  • Targeting AS represents a potential strategy to overcome pharmacoresistance in cancer therapy.
Keywords:
Alternative splicingChemoresistanceChemotherapyPharmacoresistanceSpliceosomeTumor

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