Investigation into the Role of ERK in Tyrosine Kinase Inhibitor-Induced Neuropathy

Belair DG, Sudak K, Connelly K, Collins ND, Kopytek SJ, Kolaja KL.

Toxicological Sciences, 2021



Chemotherapy-induced peripheral neuropathy is a common side effect.  Although CC-90003, a small molecule extracellular signaling kinase, elicited drug-related reversible neuropathy in dogs but not in mice.  Therefore, the authors sought to evaluate CC-90003 for phenotypic neuropathy in an in vitro assay using hiPSC-derived neurons in a multi-electrode array system.   The bioelectronic assay, with MEA plates, was sensitive to drug dosing that paralleled drug dosing clinical occurrence.  The in vitro results showed the effect on the in vivo pathway leading to neuropathy. This assays could prove useful in assessing chemotherapy-induced peripheral neuropathy.