In 2018, there were over 1.7 million new cancer diagnoses, and over 600,000 cancer related deaths in the US alone. Most people with cancer try a combination of treatments including surgery, chemotherapy and radiotherapy. Even with this combination approach, recurrence is high and the side effects are significant. Immunotherapy has tremendous potential and dramatic results have been achieved; however, it is only effective in a minority of patients and predicting treatment efficacy and patient response is challenging.
Heat Shock Protein 90 (HSP90) is a molecular chaperone protein with mitochondrial protective properties. It is used by malignant cells to support activated oncoproteins. APE1 is a DNA repair and redox factor enzyme, which is produced in response to DNA damage or upregulation of reactive oxygen species (ROS) in cells. Its purpose is to prevent cell death due to ROS mediated DNA damage. Inhibitors of HSP90 and APE1 have been studied as potential anticancer therapeutics; however, high doses are required for efficient treatment, which is associated with high toxicity.
Researchers at Arizona State University have developed novel therapeutic cocktails that have a synergistic cancer killing effect. Using different combinations of HSP90 inhibitors, APE1 inhibitors and a plasmid DNA that expresses the Granzyme A (grzA) protein, greater therapeutic efficacy was observed in cancer cells in vitro. Decreased cell viability has been demonstrated in urinary bladder cancer and ovarian cancer cell lines, and should yield similar results with other cancer types as well. These therapeutic cocktails are able to induce death in cancer cells at low concentrations without the toxicity that is typically seen with individual dosage treatments.
This combination treatment approach overcomes the challenges of monotherapies by using low doses of individual components to achieve a more synergistic therapeutic effect, while having little to no toxicity.
• Cancer treatment
o Could work on solid tumors as well as blood and bone marrow cancers
• Treatment for viral and bacterial infections
Benefits and Advantages
• Observed efficacy at decreased concentrations resulting in reduced toxicity
• Good safety profile
• GrzA induces ROS-mediated mitochondrial damage which is synergistic with HSP90 mediated inhibition
• Nearly 90% cell death observed in both UMUC3 (urinary bladder) and A2780 (ovarian) cancer cells with different combination treatments
For more information about the inventor(s) and their research, please see