2. Academic Validation
  3. A small-molecule compound cocktail for tumor reprogramming therapy for breast cancer

A small-molecule compound cocktail for tumor reprogramming therapy for breast cancer

  • Int Immunopharmacol. 2025 Jul 30:163:115273. doi: 10.1016/j.intimp.2025.115273.
Zhenyu Wang 1,  Rui Huang 2,  Jie Kong 3,  Maojia Wang 4,  Hao Yang 5,  Hongli Yan 6,  Hao Chen 7,  Yong Han 8,  Junjian Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Systems Medicine for Cancer, Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
  • 2 Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Shanghai 201620, China.
  • 3 State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 4 Department of Statistical Science, University of Toronto, Toronto M5S1A1, Canada.
  • 5 Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated with Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
  • 6 Department of Laboratory Medicine Center, Changhai Hospital, Navy Medical University, Shanghai 200433, China.. Electronic address: hongliyan@smmu.edu.cn.
  • 7 Department of Hepatobiliary Surgery, Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.. Electronic address: sj_chenh@sjtu.edu.cn.
  • 8 Department of Medical Oncology, Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.. Electronic address: hanrong2002@163.com.
  • 9 State Key Laboratory of Systems Medicine for Cancer, Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.. Electronic address: lijunjian1000@hotmail.com.
PMID: 40743622 DOI: 10.1016/j.intimp.2025.115273
Abstract

The emergence of lineage reprogramming technology has enabled us to reprogram terminally differentiated somatic cells into Other lineages. Tumor cells can reduce malignancy and even restore the function of benign cells through reprogramming technology. Establishing a tumor reprogramming system to induce tumor cell fate transformation and reduce malignancy provides a new strategy for tumor treatment. In this study, we rapidly reprogrammed breast Cancer cells with novel cocktails of small-molecule compounds, and their proliferation, metastasis, tumorigenicity, and malignancy were significantly reduced, while drug sensitivity increased, both in vitro and in vivo. Mechanistically, the cocktail may promote the transition of breast Cancer cells to Luminal subtype by downregulating the stemness-related gene TSPAN8. In summary, our results suggest that chemically induced reprogramming may be effective in the treatment of breast Cancer.

Keywords

Breast cancer; Cancer cell reprogramming; Chemical reprogramming; Differentiation therapy; Small molecule; TSPAN8.

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