Sodium channel modulation as a therapeutic strategy for chemotherapy-induced peripheral neurotoxicity

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and significant side effect of cancer treatment, triggered by exposure to widely used chemotherapeutic agents such as vinca alkaloids, taxanes, platinum-based compounds, proteasome inhibitors, thalidomide, epothilones, and antibody-drug conjugates. CIPN can be long-lasting or even permanent, leading to a decline in patients' quality of life and negatively impacting the well-being of cancer survivors. It is typically characterized by polyneuropathy or neuronopathy, primarily affecting the peripheral sensory nervous system.

Emerging evidence suggests that anticancer agents may directly alter neuronal voltage-gated sodium channels (NaV), which could play a crucial role in the development of CIPN. This review explores the mechanisms underlying CIPN, with particular focus on the potential involvement of NaV alterations. Additionally, it examines pharmacological modulators of NaV, offering key insights into the prevention of axonal damage and the management of neuropathic pain associated with CIPN.

Despite the availability of various strategies to manage CIPN, there are currently few evidence-based options for its prevention or effective treatment once it develops. As a result, CIPN remains an unmet clinical challenge, highlighting the need for further research into its underlying pathophysiological mechanisms to develop innovative therapies.