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Updated: May 20, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Targeted expression of BikDD eliminates breast cancer with virtually no toxicity in noninvasive imaging models
Xinhua Xie1, Laisheng Li, Xiangsheng Xiao
1Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, PR China.
Abstract:
Breast cancer is a major public health problem all over the world, and the current treatment strategies are not potent enough for some patients, especially those with triple-negative breast cancer. Therefore, novel and more effective treatments are critically needed. Of the current methods, targeted therapy, which not only retains cancer-specific expression but also limits toxicity, is a new strategy for treating cancers. In this study, we found that the human telomerase reverse transcriptase (hTERT; T) promoter also possesses high target specificity in breast cancer. Moreover, we developed a versatile T-based breast cancer-specific promoter VISA (VP16-Gal4-WPRE integrated systemic amplifier) composite (T-VISA) to target transgene expression in breast tumors, which has stronger activity comparable or higher than that of the cytomegalovirus promoter in cancer cells. Thereafter, targeted expression of BikDD (a mutant form of proapoptotic gene Bik) through the T-VISA platform in breast cancer initiated robust antitumor effects and prolonged survival in multiple xenograft and syngeneic orthotopic mouse models of breast tumors with virtually no toxicity in intact mice. Thus, these findings show that our T-VISA-BikDD nanoparticles effectively and safely eradicate breast cancer in vitro and in vivo and are worthy of development in clinical trials treating breast cancer.
Insights
Novel nanoparticles effectively target and eliminate breast cancer cells, including triple-negative types. This T-VISA-BikDD therapy shows significant promise for treating breast cancer with minimal toxicity.
Area of Science:
- Oncology
- Gene Therapy
- Nanotechnology
Background:
- Breast cancer remains a significant global health challenge, with current treatments insufficient for certain subtypes like triple-negative breast cancer.
- Targeted therapy offers a promising strategy by enhancing cancer specificity and reducing systemic toxicity.
- The human telomerase reverse transcriptase (hTERT) promoter demonstrates high target specificity within breast cancer cells.
Purpose of the Study:
- To develop a novel breast cancer-specific promoter composite, T-VISA, for targeted transgene expression.
- To evaluate the efficacy and safety of T-VISA-mediated delivery of the proapoptotic gene BikDD in breast cancer models.
Main Methods:
- Development of the T-VISA (VP16-Gal4-WPRE integrated systemic amplifier) composite promoter based on the hTERT promoter.
- Utilizing the T-VISA platform to drive expression of BikDD (a mutant proapoptotic Bik gene).
- Testing T-VISA-BikDD nanoparticles in in vitro and in vivo mouse models (xenograft and orthotopic) of breast cancer.
Main Results:
- The T-VISA promoter exhibited strong activity in cancer cells, comparable or superior to the cytomegalovirus promoter.
- Targeted expression of BikDD via T-VISA demonstrated robust antitumor effects and prolonged survival in breast cancer models.
- T-VISA-BikDD nanoparticles showed effective and safe eradication of breast cancer with no observed toxicity in healthy mice.
Conclusions:
- The T-VISA-BikDD nanoparticle system provides an effective and safe strategy for targeting and eliminating breast cancer.
- These findings support the further development of T-VISA-BikDD for clinical trials in breast cancer treatment.
