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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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CD44 variant exons induce chemoresistance by modulating cell death pathways.

Maria Yanova1, Evgeniya Stepanova1, Diana Maltseva1

  • 1Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia.

Frontiers in Cell and Developmental Biology
|March 21, 2025
PubMed
Summary

Cancer chemoresistance is a major challenge, but CD44 variant exons are emerging as key players. Understanding their role in cell death pathways offers new hope for targeted cancer therapies.

Keywords:
CD44 variant exon 6CD44 variant exon 9apoptosisautophagycancerchemoresistanceferroptosis

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chemoresistance in cancer leads to treatment failure.
  • CD44, a cell surface glycoprotein, is implicated in cancer biology.
  • CD44 variant exons are linked to chemoresistance and cancer progression.

Purpose of the Study:

  • To analyze the association of CD44 variant exons with patient chemotherapy outcomes.
  • To explore the role of CD44 variant exons in modulating cancer cell death pathways.
  • To review clinical trials targeting CD44 variant exon isoforms.

Main Methods:

  • Comprehensive literature review on CD44 variant exons and clinical outcomes.
  • Analysis of CD44's role in apoptosis, ferroptosis, and autophagy.
  • Examination of CD44-targeted therapeutic strategies and clinical trials.

Main Results:

  • Specific CD44 variant exons (e.g., v6, v9) significantly impact patient chemotherapy outcomes.
  • CD44 variant exons modulate key cell death pathways, influencing drug resistance.
  • Variant exon-containing CD44 isoforms are associated with clinical outcomes.

Conclusions:

  • CD44 variant exons are critical determinants of chemoresistance and patient prognosis.
  • Targeting CD44 variant exon isoforms presents a promising therapeutic strategy.
  • Further research into CD44-targeted therapies could overcome cancer drug resistance.