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Updated: Sep 26, 2026

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
[Gene therapy for breast cancer]
Shunji Takahashi1, Kiyohiko Hatake, Yoshikazu Sugimoto
1Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.
Abstract:
Breast cancer is sensitive to chemotherapy and endocrine therapy, but the prognosis of advanced or relapsed breast cancer is unsatisfactory. Gene therapy is promising as another useful therapeutic approach for advanced breast cancer. Strategies of gene therapy for breast cancer in ongoing clinical protocols can be divided into four: (1) suppression of oncogenes or transduction of tumor suppressors; (2) enhancement of immunological response to cancer cells; (3) transduction of suicide genes; and (4) protection of bone marrow using drug resistance genes. We have started a clinical study of gene therapy for breast cancer using multidrug resistance gene (MDR1), in which advanced or relapsed breast cancer patients received high dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT) with MDR1-transduced hemopoietic cells, and then were treated with docetaxel. Two patients have been treated so far, and in vivo enrichment of MDR1-transduced cells with docetaxel treatment after PBSCT was seen in both cases. Both patients are in complete remission and have no apparent adverse effect from MDR1 gene transduction.
Insights
Gene therapy using the multidrug resistance gene (MDR1) shows promise for advanced breast cancer. Two patients achieved complete remission with no adverse effects after high-dose chemotherapy and MDR1-transduced stem cell transplantation.
Area of Science:
- Oncology
- Gene Therapy
- Hematology
Background:
- Advanced or relapsed breast cancer prognosis remains poor despite chemotherapy and endocrine therapy.
- Gene therapy presents a promising therapeutic avenue for advanced breast cancer.
- Current gene therapy strategies include oncogene suppression, immune enhancement, suicide gene transduction, and drug resistance gene transfer.
Purpose of the Study:
- To evaluate the safety and efficacy of multidrug resistance gene (MDR1) therapy in patients with advanced or relapsed breast cancer.
- To assess the in vivo enrichment of MDR1-transduced cells following high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT).
Main Methods:
- A clinical study involving advanced or relapsed breast cancer patients undergoing high-dose chemotherapy and autologous PBSCT with MDR1-transduced hemopoietic stem cells.
- Post-transplantation treatment with docetaxel to promote enrichment of MDR1-transduced cells.
- Monitoring for complete remission and adverse effects.
Main Results:
- Two patients were treated, both exhibiting in vivo enrichment of MDR1-transduced cells after docetaxel treatment post-PBSCT.
- Both patients achieved complete remission.
- No apparent adverse effects were observed from the MDR1 gene transduction.
Conclusions:
- MDR1 gene therapy combined with high-dose chemotherapy, PBSCT, and docetaxel is a potentially effective treatment for advanced or relapsed breast cancer.
- This approach demonstrated successful in vivo cell enrichment and achieved complete remission in treated patients.
- The treatment appears safe with no significant adverse effects related to MDR1 gene transduction.
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