Grant: CIHR - ICR / Cancer Research Society Partnership - Res. Grants - Breast Cancer

Serious adverse effects of specific cancer drugs often limit their clinical use leaving patients with poor treatment choices. Cisplatin (CP) is a treatment choice for triple-negative breast cancer and BRCA1 inactive breast cancer. Unfortunately, CP affects nerve functions, resulting in ‘peripheral neuropathy’, manifested by severe pain, numbness, lack of spatial awareness, and movement defects. Several other anticancer drugs also induce treatment-limiting neuropathy, and currently, no effective therapies are available for drug-induced neuropathy. Our preliminary RNA sequencing study revealed that several biomolecules in neurons change their expression during the development CP induced peripheral neuropathy (CisIPN). We also found that breast cancer (BC) increases the severity of CisIPN underscoring the importance of factoring BC while evaluating potential therapies for CisIPN in BC patients. Therefore, in this study, we will test the effect of ten molecular hits selected from our RNA-sequencing studies for their effect on CisIPN in a BC animal model (aim 1). Our preliminary studies showed that the potent anti-inflammatory drug Dexamethasone partially protects BC animals from CisIPN. Therefore, we will also test the effects of combinations of Dex and the most potent three candidate approaches identified from aim 1 on CisIPN in a BC animal model (aim 2). Overall, we hope to identify new therapeutic approaches for managing CisIPN in BC.