Federal Grant Award Summary

The National Cancer Institute (NCI) awarded a $410,545 Project Grant through the Cancer Treatment Research program (CFDA 93.395) to The Research Foundation for the State University of New York to conduct a two-year research initiative (May 1, 2026 – April 30, 2028) addressing monomethyl auristatin E (MMAE)-induced peripheral neuropathy in antibody-drug conjugate (ADC) cancer therapy. The research focuses on identifying novel signaling pathways and evaluating the role of membrane transporters, particularly P-glycoprotein (P-GP), in regulating MMAE-induced neurotoxicity that affects approximately 50% of treated patients. This investigation aims to uncover pharmacological targets to mitigate neurological side effects and predict interpatient variability through genetic variation or drug interactions.

The project employs two primary research approaches: evaluation of P-GP as a regulator of MMAE pharmacokinetics and peripheral nerve disposition using in vivo and ex vivo P-GP genetic knockout mouse models, and identification of signaling changes in peripheral nerves through systems pharmacology network-based modeling. The anticipated deliverables include characterization of transporter function in MMAE disposition, comprehensive analysis of molecular and cellular signaling pathways associated with MMAE-induced neuropathy, and identification of combination therapeutic targets to abolish or mitigate this devastating adverse event while improving cancer treatment outcomes and quality of life for patients receiving ADC-based therapies.