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Targeting RPRD1B overcomes chemoresistance in gastric cancer by suppressing the TOPBP1-mediated DNA damage repair

Jian Sheng1,2, Jianghua Li1, Chenxi Cao3

  • 1School of Basic Medical Sciences, Tsinghua University, Beijing, China.

Cellular Oncology (Dordrecht, Netherlands)
|August 1, 2026
PubMed
Abstract

Insights

High RPRD1B expression in gastric cancer predicts poor response to 5-fluorouracil (5-FU) chemotherapy. Targeting RPRD1B with AAV-delivered shRNA overcomes this resistance by upregulating TOPBP1, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • 5-fluorouracil (5-FU) resistance is a major challenge in gastric cancer (GC) treatment.
  • RPRD1B (CREPT) is overexpressed in GC, linked to poor prognosis and aggressive phenotypes.
  • The role of RPRD1B in mediating chemotherapy resistance remained unclear.

Purpose of the Study:

  • To elucidate the role of RPRD1B in 5-FU resistance in gastric cancer.
  • To investigate the molecular mechanisms underlying RPRD1B-mediated chemoresistance.
  • To develop a therapeutic strategy targeting RPRD1B to overcome 5-FU resistance.

Main Methods:

  • Established 5-FU-resistant gastric cancer cell lines.
  • Investigated the correlation between RPRD1B and TOPBP1 expression.
  • Utilized an adeno-associated virus (AAV)-based system for RPRD1B knockdown in vivo.

Main Results:

  • High RPRD1B tumor expression correlated with poor response to 5-FU chemotherapy in GC patients.
  • RPRD1B expression positively correlated with TOPBP1, a DNA damage repair effector.
  • RPRD1B transcriptionally upregulates TOPBP1, enhancing DNA damage repair and mediating chemoresistance.
  • AAV-delivered shRNA targeting RPRD1B effectively overcame 5-FU resistance in a mouse xenograft model.

Conclusions:

  • RPRD1B plays a critical role in mediating 5-FU resistance in gastric cancer.
  • RPRD1B is a promising therapeutic target for reversing chemoresistance.
  • Targeting RPRD1B offers a potential strategy to improve 5-FU efficacy in gastric cancer treatment.
Keywords:
5-FUAAVDNA damage repairRPRD1B

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