June 18, 2020
Platinum chemotherapeutics such as oxaliplatin are among the most effective anticancer agents, but their clinical use is associated with severe damage to peripheral nerves (neurotoxicity).
Using unique genetically engineered mouse and rat models, Kevin Huang, a graduate student at the College of Pharmacy, and his mentors, Shuiying Hu, PhD, and Alex Sparreboom, PhD, from the Division of Pharmaceutics and Pharmacology, reported in the Journal of Clinical Investigation that this toxicity is dependent on a transporter-mediated uptake process.
The identified transport system can be inhibited by the tyrosine kinase inhibitor dasatinib, and pretreatment with this agent can prevent neurotoxicity in mice without negatively affecting anticancer properties.
"The significance of these findings is that we identified a novel intervention strategy to prevent oxaliplatin neurotoxicity in rodent models, and we hope for the continued success of this project as it moves from the benchtop and into cancer patients," Huang said. "Drs. Shuiying and Sparreboom have been nothing short of amazing mentors by providing me with endless support throughout my graduate career. They deserve equal recognition and acknowledgment."
The clinical relevance of this concept is currently being explored in patients with colorectal cancer in collaboration with medical oncologists at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.