Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonly used drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.
Highlights
Cancer is currently a leading cause of mortality worldwide [1]
In the subsequent part of this paper, we review the clinical picture of chemotherapy-induced peripheral neuropathy (CIPN) and the exact neurotoxicity mechanisms associated with individual drugs most commonly used in cancer chemotherapy, namely, platinum-based antineoplastics, immunomodulatory drugs, taxanes, epothilones, vinca alkaloids and proteasome inhibitors
The TRPA1 (TRP ankyrin), TRPV1 (TRP vanilloid) and TRPM8 (TRP melastatin) channels are expressed in DRG neurons, and a few preclinical studies have shown that they play a crucial role in cold and mechanical sensitivity induced by oxaliplatin and cisplatin
Summary
Cancer is currently a leading cause of mortality worldwide [1]. thanks to advances in medicine and modern technology, the availability of sensitive tests and diagnostic methods to detect cancer at an early stage and the use of increasingly effective treatments, including chemotherapeutic agents, the number of cancer survivors is rising: It is expected to increase by 35%, from 13.7 million in 2012 to 18 million, by 2022 [2]. Six main agent groups cause damage to the peripheral sensory, motor and autonomic neurons, resulting in CIPN development: platinum-based antineoplastics ( oxaliplatin and cisplatin), vinca alkaloids ( vincristine and vinblastine), epothilones (ixabepilone), taxanes (paclitaxel, docetaxel), proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide) [12]. The most important risk factors of acute and chronic OIPN include the cumulative oxaliplatin dose, the 2 h time of infusion, low body weight, younger age, a body surface area > 2,0, gene variations (GSTP1, glutathione-S-transferase genes P1; GSTM1, glutathione-S-transferase genes M1; and voltage-gated sodium channel genes SCN4A, SCN9A and SCN10A) and peripheral neuropathy symptoms prior to chemotherapy [41,42,43,44]. Some of these mechanisms are discussed in more detail below
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