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Published July 2023 | public
Journal Article

Calcium signaling in chemotherapy-induced neuropathy


Alterations in calcium (Ca²⁺) signaling is a major mechanism in the development of chemotherapy-induced peripheral neuropathy (CIPN), a side effect caused by multiple chemotherapy regimens. CIPN is associated with numbness and incessant tingling in hands and feet which diminishes quality of life during treatment. In up to 50% of survivors, CIPN is essentially irreversible. There are no approved, disease-modifying treatments for CIPN. The only recourse for oncologists is to modify the chemotherapy dose, a situation that can compromise optimal chemotherapy and impact patient outcomes. Here we focus on taxanes and other chemotherapeutic agents that work by altering microtubule assemblies to kill cancer cells, but also have off-target toxicities. There have been many molecular mechanisms proposed to explain the effects of microtubule-disrupting drugs. In neurons, an initiating step in the off-target effects of treatment by taxane is binding to neuronal calcium sensor 1 (NCS1), a sensitive Ca²⁺ sensor protein that maintains the resting Ca²⁺ concentration and dynamically enhances responses to cellular stimuli. The taxane/NCS1 interaction causes a Ca²⁺ surge that starts a pathophysiological cascade of consequences. This same mechanism contributes to other conditions including chemotherapy-induced cognitive impairment. Strategies to prevent the Ca²⁺ surge are the foundation of current work.

Additional Information

© 2023 Elsevier. This work was supported by CNPq, CAPES, FAPEMIG, FAPESP (2019/13112-8) and INCT-Nanobiofar (Brazil). Author contribution statement: Conceptualization, writing, reviewing, and editing: MCF, PHSMD, MFL and BEE. CRediT authorship contribution statement: Matheus de Castro Fonseca: Conceptualization, Writing – original draft, Writing – review & editing, Funding acquisition. Paulo H S Marazzi-Diniz: Conceptualization, Writing – original draft, Writing – review & editing. M Fatima Leite: Conceptualization, Writing – original draft, Writing – review & editing, Funding acquisition. Barbara E Ehrlich: Conceptualization, Writing – original draft, Writing – review & editing, Funding acquisition. Declaration of Competing Interest: BEE is a founder and shareholder of Osmol Therapeutics, a company that is targeting NCS1 for therapeutic purposes. Data availability: No data was used for the research described in the article.

Additional details

August 22, 2023
October 20, 2023