Review of the contribution of clinical and genetic factors to the racial disparity in taxane-induced peripheral neuropathy

Taxanes are first-line chemotherapy for several solid tumors, but their use is often limited by taxane-induced peripheral neuropathy (TIPN), which can cause acute symptoms in up to 70 % of patients and severely deteriorate long-term quality of life. Recent evidence from large prospective observational studies confirms a dramatic racial disparity, with Black/African-ancestry patients facing roughly two times greater risk of TIPN compared to White patients. Understanding the root causes of this disparity is a critical first step toward eliminating inequities in cancer treatment side effects, aligning with a major goal of the U.S. National Cancer Institute's National Cancer Plan. This review examines clinical and genetic factors contributing to racial differences in TIPN, focusing on those that have been associated with TIPN risk and are more prevalent within Black/African-ancestry individuals. Pre-existing neuropathy, vitamin D insufficiency, metabolic risk factors (obesity/diabetes), systemic taxane exposure, and genetic variants are discussed as potential contributors to this racial disparity. The review concludes by describing additional research that is needed to determine which of these factors are responsible for this disparity and what types of translational clinical studies could be conducted to target these mechanisms and reduce inequity. These findings could inform clinical strategies that improve long-term quality of life and promote health equity in taxane-treated cancer patients in the U.S. and globally.