Therapeutic Benefit of Potassium Channel Activators in Triple-Negative Breast Cancer
Abstract
Our project is designed to address the following overarching challenges: (1) Eliminating the mortality associated with triple-negative breast cancer (TNBC) and (2) replacing drugs with life-threatening toxicities with safe, effective interventions. TNBC is a biologically aggressive form of breast cancer (BC) with the worst outcome of all BC subtypes. TNBC is a significant contributor to cancer disparities since African-American women are twice as likely as are women from other racial groups to develop TNBC. Current treatment approaches for TNBC are unsatisfactory since they result in high rates of recurrence and death despite optimal therapy. Lack of therapies precisely target vulnerabilities in cancer cells (targeted therapy) has impeded progress in this disease subtype, and it has limited the therapeutic armamentarium to chemotherapy drugs that negatively impact quality of life. During our investigation to identify new targeted approaches for cancer treatments that are effective and safe, we identified a new target in TNBC. This target is called Kv11.1 potassium ion channel. When Kv11.1 is activated by drugs, tumor growth in mice is inhibited. Importantly, Kv11.1 activators are well tolerated in mice and do not generate significant side effects. Also, we found that in mice these drugs increase the effectiveness of chemotherapy drugs that are currently used to treat TNBC. These results are significant because they suggest that Kv11.1 activators could result in more effective treatment when given with chemotherapy and at the same time reduce toxicity by allowing treatment with lower doses of the chemotherapy. Therefore, we propose to expand our preliminary research to evaluate the potential therapeutic benefit of the Kv11.1 activators in TNBC more thoroughly. For this study, we will investigate Kv11.1 activators in TNBC tumors that were obtained directly from patients and implanted into mice, which are the best predictors of what will happen in patients. The proposed studies are a key step in translating our innovative approach into an effective treatment strategy that improves survival and reduces treatment-related side effects for women with the type of breast cancer that is the most difficult to treat.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010467
Entities
People
- Kent Hoskins
Organizations
- United States Army
- University of Illinois at Chicago