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Updated: Nov 3, 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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Emerging Roles of SKP2 in Cancer Drug Resistance

Ting Wu1, Xinsheng Gu2, Hongmei Cui1

  • 1Institute of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China.

Cells
|June 2, 2021
PubMed

Insights

Chemotherapy resistance is a major hurdle in cancer treatment. This review highlights how S-phase kinase-associated protein 2 (Skp2) drives this resistance and explores potential therapeutic strategies targeting Skp2.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Chemotherapy resistance significantly limits treatment efficacy in over half of cancer patients.
  • S-phase kinase-associated protein 2 (Skp2), an E3 ligase, is increasingly recognized as a key factor in chemoresistance and poor patient prognosis.

Purpose of the Study:

  • To review the multifaceted mechanisms by which Skp2 contributes to chemotherapy resistance.
  • To explore novel therapeutic strategies targeting Skp2 for improved cancer treatment outcomes.

Main Methods:

  • Literature review summarizing research on Skp2 and its role in cancer drug resistance.
  • Analysis of molecular pathways implicated in Skp2-mediated resistance, including feedback loops, cell cycle regulation, and DNA repair.
  • Identification and discussion of emerging therapeutic agents targeting Skp2.

Main Results:

  • Skp2 promotes drug resistance through various mechanisms, including the Akt-Skp2 feedback loop and regulation of the Skp2-p27 pathway.
  • Skp2 influences cell cycle progression, mitosis, epithelial-mesenchymal transition (EMT), and DNA damage response, all contributing to resistance.
  • Several novel molecules inhibiting Skp2 expression or its interactions show promise for clinical application.

Conclusions:

  • Skp2 is a critical mediator of chemotherapy resistance across various cancers.
  • Targeting Skp2 and its associated pathways represents a promising therapeutic avenue to overcome drug resistance and improve patient response to chemotherapy.
Keywords:
AktDNA damage response and repairEMTSkp2cell cycledrug resistanceinhibitorsmitosisp27

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