Prevention of Chemotherapy-Induced Peripheral Neuropathy by Modulation of Cellular Membrane Transport and Intracellular Unbound Drug Exposure (PreventCIPN)

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious and common adverse event after cancer treatment. Multiple molecular mechanisms are linked to CIPN-sites in the peripheral nervous system.

Recently federated knowledge on the potential role of membrane transporters in governing accumulation of drugs in CIPN-sites opens up new perspectives in investigating innovative pharmacokinetics-based approaches to prevent CIPN by modulation of drug transporter function.

With PreventCIPN we aim to: 1) Provide systematic quantitative assessment of CIPN-causing drugs (CIPN-D) transport across endothelial and parenchymal cellular barriers at key CIPN-sites following acute and chronic administration to rats, utilizing unique methodologies developed in our group, 2) Identify membrane transporters that contribute to specific accumulation of CIPN-D and confirm their involvement using phenotypic screening in in vitro and in vivo models supported by targeted proteomics and quantitative mass spectrometry imaging; 3) Perform randomized, blinded preclinical trials in rats using selected novel CIPN-D - transporter modulator combinations and validate their effectiveness in preventing CIPN, supported by pharmacokinetic analysis, histopathological examination and biomarker profiling.

The team of experts unites their complementary knowledge and expertise, achieving a critical mass of multidisciplinarity to investigate the intricate pharmacokinetic mechanisms for combating CIPN.