Program Official

Principal Investigator

Ohannes Kevork
Awardee Organization

University Of Maryland Baltimore
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Eligible
Project End Date

Identification of novel targets for the treatment of chemotherapy-induced painful peripheral neuropathy

Chemotherapy-induced painful peripheral neuropathy (CIPN) is the most common toxicity associated with widely used chemotherapeutics. CIPN is the major cause of dose reduction or discontinuation of otherwise life-saving treatment. Unfortunately, CIPN can persist in cancersurvivors which adversely affects their quality of life. Moreover, available treatments are vastly inadequate which necessitates the development of novel mechanism-based therapies that can either prevent or treat CIPN. Recently, HIF1A, PDHK1, and LDHA have been demonstrated to be the key molecular mediators that initiate and maintain bortezomib-induced neuropathic pain. However, those studies were carried out in tumor-free mice. Moreover, our preliminary results also implicate those molecular targets in paclitaxel and oxaliplatin-induced neuropathic pain. Hence, the objective of this proposal is to validate that HIF1A, PDHK1 and LDHA are shared mediators that lead to the development and maintenance of bortezomib, paclitaxel and oxaliplatininduced neuropathic pain in tumor-bearing mice. Using biochemical, metabolic, behavioral and innovative imaging method of intact DRGs this application aims to systematically validate these targets for the prevention and treatment of CIPN. Successful completion of this project promises to lower the risk of adopting these targets in translational projects to develop novel non-addictive therapeutics for chemotherapy-induced neuropathic pain.


  • Kuppusamy P, Haque MM, Traub RJ, Melemedjian OK. Targeting metabolic pathways alleviates bortezomib-induced neuropathic pain without compromising anticancer efficacy in a sex-specific manner. Frontiers in pain research (Lausanne, Switzerland). 2024 Jun 24;5:1424348. doi: 10.3389/fpain.2024.1424348. eCollection 2024. PMID: 38979441