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Updated: Jul 26, 2025

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A targetable pathway to eliminate TRA-1-60+/TRA-1-81+ chemoresistant cancer cells

Lei Tan1,2, Xiaohua Duan1,3, Pratyusha Mutyala1

  • 1Department of Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Journal of Molecular Cell Biology
|June 16, 2023
PubMed

Insights

Researchers identified TRA-1-60 and TRA-1-81 as key cell surface markers on chemoresistant pancreatic cancer cells. Targeting these markers with compounds like Cymarin may offer new therapeutic strategies to overcome treatment failure.

Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Discovery

Background:

  • Chemoresistance significantly limits treatment efficacy in pancreatic cancer.
  • Identifying specific markers on chemoresistant cancer cells (CCCs) is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify novel cell surface markers associated with chemoresistance in pancreatic cancer.
  • To elucidate the molecular mechanisms underlying chemoresistance.
  • To discover potential therapeutic agents to overcome chemoresistance.

Main Methods:

  • Antibody-based screening to identify cell surface markers on CCCs.
  • Transcriptome profiling to understand gene expression in CCCs.
  • High-content chemical screening to identify drug candidates.
  • In vitro and in vivo validation of therapeutic agents.

Main Results:

  • TRA-1-60 and TRA-1-81 were identified as highly enriched 'stemness' cell surface markers on CCCs.
  • UGT1A10 was found to be essential for maintaining TRA-1-60/TRA-1-81 expression and chemoresistance.
  • Cymarin, a novel compound, downregulated UGT1A10, reduced TRA-1-60/TRA-1-81 expression, and enhanced chemosensitivity.
  • TRA-1-60/TRA-1-81 expression correlated with chemoresistance and poor survival in primary pancreatic tumors.

Conclusions:

  • TRA-1-60/TRA-1-81 are novel, specific cell surface markers for chemoresistant pancreatic cancer cells.
  • The UGT1A10 pathway is critical for maintaining chemoresistance.
  • Cymarin shows promise as a therapeutic agent to target this pathway and improve treatment outcomes.
Keywords:
CymarinTRA-1-60/TRA-1-81UGT1A10chemoresistancepancreatic cancer

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