Emerging roles of toll-like receptor 4 in chemotherapy-induced neurotoxicity

Abstract

Chemotherapy-induced neurotoxicity is one of the most prevalent side effects in cancer patients and survivors. Cognitive decline and peripheral neuropathy are the most common chemotherapy-induced neurotoxic symptoms. These symptoms lead not only to the limiting of the dose of chemotherapy given to cancer patients, but also have an impact on the quality of life of cancer survivors. Although the exact mechanisms involved in chemotherapy-induced neurotoxicity are still unclear, neuroinflammation is widely regarded as being one of the major causes involved in chemotherapy-induced neurotoxicity. It is known that Toll-like receptor 4 (TLR4) plays a critical role in the inflammatory process, and it has been recently reported that it is associated with chemotherapy-induced neurotoxicity. In this review, we summarize and discuss all available evidence regarding the activation of the TLR4 signaling pathway in various models of chemotherapy-induced neurotoxicity. This review also emphasizes the evidence pertinent to TLR4 inhibition on chemotherapy-induced neurotoxicity in rodent studies. Understanding the role of the TLR4 signaling pathway behind chemotherapy-induced neurotoxicity is crucial for improving treatments and ensuring the long-term survival of cancer patients.