Damian Sendler: Among cancer survivors, chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect. There is still a lack of effective CIPN preventative and treatment options. A better knowledge of CIPN's etiology may open up new avenues for the development of a better treatment plan.

Toxic chemotherapeutic treatments frequently cause chemotherapy-induced peripheral neuropathy (CIPN). Patients who have had cancer may suffer from long-term morbidity as a result of this condition. CIPN's prevalence and burden are predicted to rise as cancer survival rates improve.  

Damian Jacob Sendler: Nearly half of all cancer survivors (47%) experienced neuropathy for at least six years after completing chemotherapy. Changes in gait patterns were evident in patients with CIPN, with slower and shorter steps and an 18-fold increase in fall risk . Furthermore, it was found that 13% of cancer survivors with CIPN died within three months . To improve cancer survivors' quality of life and safety, an effective treatment for CIPN is needed.

Damian Sendler

There are currently no treatments for preventing CIPN. Chemotherapeutics for CIPN management are hindered by the lack of a defined target. New strategies for prevention and therapy could be developed with an understanding of how CIPN develops and evolves . As a result, it remains a challenge to transfer the mechanistic understandings into clinical interventions that will lead to the creation of novel effective techniques . However, a well-designed study based on known pathways can assist solve the unmet medical need. Based on the results of clinical trials in Western medicine as well as complementary and alternative medicine, this review highlights the current understanding of CIPN and current recommendations for treatment.

Neurotoxic side effects of chemotherapy for breast, gastric, gynecologic, and hematologic cancers are prevalent and painful, and CIPN is one of the most common. It will become more common as cancer survival rates improve. Chemotherapy-induced nausea and vomiting affects more than 68% of patients . Traditional chemotherapeutics, including platinum analogs, antimitotic drugs (taxanes and vinca alkaloids), and proteasome inhibitors, have a greater risk of CIPN . Within the first two months of treatment, typical CIPN symptoms emerge.

In the course of chemotherapy, CIPN gets worse, but stabilizes once treatment is through. But many patients have unrelenting pain, tightness, and numbness in their limbs. These symptoms can have a negative impact on sleep, emotions, and quality of life. Even though the majority of CIPN is dose-dependent, other drug-specific syndromes, such as paclitaxel- and oxaliplatin-induced acute neurotoxicity or cisplatin cessation that worsened neuropathy, have been documented as well. These include

Damien Sendler: The peripheral nervous system (PNS) is more susceptible to CIPN than the central nervous system because of the lack of a blood–brain barrier and excellent lymphatic drainage . Furthermore, sensory neurons are easier to penetrate than motor neurons because they have less myelination . A wide range of alterations can be seen, from changes in ion channel activity to changes in intracellular signaling networks.

Damian Jacob Sendler 

Mitochondrial malfunction, redox homeostasis imbalance, inflammation, and nerve degeneration are all common pathogenic processes . There is a wide range of variability in the types of drugs, dosages, side effects, and onset of neuropathic symptoms across patients. CIPN's development may be influenced by the manner in which it is administered. Only intrathecal injection of methotrexate is likely to cause neurotoxicity . Subcutaneous treatment of bortezomib can minimize the development of CIPN . Gene-environment interactions may also be influenced by genetic variants, which could serve as biomarkers for CIPN prediction .

PNS damage causes macrophage and Schwann cell migration into the lesions to remove debris, followed by the release of neurotrophic factors from these cells to encourage neuroregeneration. Stimulator of Interferon Genes (STING)–Interferon Type I (IFN-I) signaling axis was recently found to be important regulator of physiological pain and prospective target for the treatment of CIPN. CIPN has been linked to the secretion of galactin-3 by Schwann cells .

Damian Jacob Markiewicz Sendler: Neurotoxic chemotherapies include a variety of mechanisms, but they may be closely linked to their principal functions in anticancer effects. Platinum drugs, such as cisplatin and oxaliplatin, can cause mitochondrial malfunction and neuronal death in the dorsal root ganglia by DNA cross-linking or oxidative stress. To further extend neuronal depolarization and hyperexcitability, the oxalate metabolized from oxaliplatin prolongs the open state of the voltage-gated sodium channel. CIPN-infected cells do not divide, unlike cancer cells, which do. 

Proteostasis imbalances between cancer cells and non-dividing neuronal cells, pointing to a route to simultaneously lengthen neuronal cell survival by improving protein refolding in order to eliminate DNA adducts via the DNA repair process, have been identified in this study.

Dr. Damian Jacob Sendler and his media team provided the content for this article.