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Updated: May 9, 2025

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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TFDP1 drives triple-negative breast Cancer development through senescence suppression and serves as a therapeutic

Gaoda Ju1, Qingliang Lin1, Lihu Lu1

  • 1Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou 350001, Fujian Province, China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors, Fujian Medical University, Fuzhou 350001, Fujian Province, China; Digestive, Hematological and Breast Malignancies, Clinical Research Center for Radiology and Radiotherapy of Fujian Province, Fuzhou 350001, Fujian Province, China.

International Journal of Biological Macromolecules
|April 29, 2025
PubMed

Insights

Topotecan targets TFDP1 to inhibit triple-negative breast cancer (TNBC) growth and promote senescence. This discovery offers a new therapeutic strategy for TNBC by targeting TFDP1 and combining topotecan with senolytic treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Triple-negative breast cancer (TNBC) has the poorest prognosis among breast cancer subtypes.
  • Targeted therapies are crucial for improving outcomes in TNBC patients.
  • Understanding molecular targets and mechanisms is essential for reducing TNBC mortality.

Purpose of the Study:

  • To identify therapeutic targets and mechanisms of action for topotecan in triple-negative breast cancer.
  • To investigate the role of TFDP1 in TNBC progression and its potential as a therapeutic target.
  • To explore the combined therapeutic potential of topotecan and senolytic agents for TNBC.

Main Methods:

  • CRISPR/Cas9 library screening to identify potential therapeutic targets in TNBC.
  • Utilizing the L1000FWD database to link topotecan to potential targets.
  • In vitro experiments including gene knockdown, cell growth assays, and senescence analysis.

Main Results:

  • TFDP1 was identified as a potential therapeutic target in TNBC, with its overexpression correlating with poorer prognosis.
  • Knockdown of TFDP1 inhibited TNBC cell growth, proliferation, and tumorigenicity.
  • Topotecan was shown to inhibit TNBC cell growth and induce cellular senescence, counteracting TFDP1 overexpression effects.

Conclusions:

  • Topotecan impedes TNBC cell growth by targeting TFDP1, offering insights into TNBC cell senescence mechanisms.
  • TFDP1 represents a promising therapeutic target for triple-negative breast cancer.
  • Combining topotecan with senolytic therapies may provide a novel and effective treatment strategy for TNBC.
Keywords:
TFDP1TopotecanTriple-negative breast cancer

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