Small molecule inhibitor doxorubicin hydrochloride (Dox) conjugated to reovirus for targeted combination therapy of triple-negative breast cancer (TNBC).
- Targeted treatment that directly infects and kills breast cancer cells.
- Increased cytopathicity, cytotoxicity and faster induction of cell death than virus alone.
- Enhanced selective delivery of doxorubicin to TNBC cells.
Triple-negative breast cancer (TNBC) is when the breast cancer cells lack the three most common receptors known to fuel breast cancer growth—estrogen, progesterone, and hormone epidermal growth factor receptor 2 (HER-2). TNBC constitutes approximately 15% of all breast cancer, has a higher rate of relapse, and shorter overall survival after metastasis than other subtypes of breast cancer. Since the tumor cells lack the receptors targeted by common treatments like hormone therapy, receptor-specific drugs are ineffective. Current therapies for TNBC are surgical removal of tumor, non-specific cytotoxic chemotherapy, and radiation. Chemotherapy and radiation can cause significant side-effects including damage to healthy cells and tissue.
Emory University and Children’s Healthcare of Atlanta researchers have engineered multiple constructs of reovirus with enhanced attachment, infectivity, and ability to induce cell death in Triple-Negative Breast Cancer (TNBC) cells. The researchers have also developed a combination therapy for TNBC treatment by conjugation of small molecule inhibitor doxorubicin hydrochloride (Dox) to reovirus (Reo-dox). In several TNBC cells, Reo-dox robustly enhanced TNBC cell killing without affecting the ability of the virus to infect and replicate. Reo-dox induces DNA double-strand break damage at similar levels as doxorubicin alone. Together, these findings show that this conjugation provides a potent therapeutic method to directly target and kill cancer cells while minimizing toxicity to healthy cells and tissues in a multi-faceted combinatorial approach.
Doxorubicin-conjugated reovirus has been synthesized and successfully tested yielding clinically significant results.
Berry, J. T. et al. (2019). AACR Annual Meeting 2019; Cancer Res 2019; 79(13 Suppl): Abstract no. 2169.