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Updated: Aug 19, 2026

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
[Gene therapy for breast cancer]
Shunji Takahashi1, Yoshikazu Sugimoto
1Department of Medical Oncology, Cancer Institute Hospital.
Abstract:
Gene therapy for advanced breast cancer is expected to be useful therapeutic approach. Strategies in ongoing clinical protocols can be divided into four: (1) suppression of oncogenes or transduction of tumor suppressor genes; (2) enhancement of immunological response; (3) transduction of suicide genes; (4) protection of bone marrow using drug resistance gene. We have started clinical study of multidrug resistance (mdr1) gene therapy. Advanced breast cancer patients received high dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT) with mdr1-transduced hematopoietic cells, and then were treated with docetaxel. 2 patients have been treated so far, and in vivo enrichment of mdr1-transduced cells with docetaxel treatment was seen. Both patients are in complete remission and have no apparent adverse effect from mdr1 gene transduction.
Insights
Gene therapy using the multidrug resistance (mdr1) gene shows promise for advanced breast cancer. Patients receiving mdr1-transduced cells and docetaxel achieved complete remission with no adverse effects.
Area of Science:
- Oncology
- Gene Therapy
- Hematopoietic Stem Cell Transplantation
Context:
- Advanced breast cancer presents significant treatment challenges.
- Current gene therapy strategies include oncogene suppression, immune enhancement, suicide gene transfer, and drug resistance gene therapy.
- Multidrug resistance (mdr1) gene therapy is being investigated as a protective measure against high-dose chemotherapy.
Purpose:
- To evaluate the safety and efficacy of multidrug resistance (mdr1) gene therapy in patients with advanced breast cancer.
- To assess the in vivo enrichment of mdr1-transduced hematopoietic stem cells following high-dose chemotherapy and docetaxel treatment.
- To determine the therapeutic potential of combining mdr1 gene therapy with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT).
Summary:
- A clinical study involving advanced breast cancer patients undergoing high-dose chemotherapy and autologous PBSCT with mdr1-transduced hematopoietic cells was initiated.
- Two patients received docetaxel treatment post-transplantation, demonstrating in vivo enrichment of mdr1-transduced cells.
- Both treated patients achieved complete remission with no observed adverse effects related to the mdr1 gene transduction.
Impact:
- mdr1 gene therapy, combined with high-dose chemotherapy and PBSCT, offers a potentially effective treatment for advanced breast cancer.
- This approach may enhance treatment tolerance by protecting bone marrow from chemotherapy-induced toxicity.
- The findings support further clinical investigation of mdr1 gene therapy in breast cancer and potentially other malignancies.
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