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= Neurotoxicity of Chemotherapy Drugs = Chemotherapy is a widely used treatment for cancer. Chemotherapy drugs are intrinsically cytotoxic chemicals targeting on perturbating cell division or mitosis of the actively proliferating cells. Such perturbation will further induce DNA damage and, ultimately, the cell death (apoptosis) of the cancer cells. Since cells in normal tissue are not as actively dividing as cancer cells, they are much less influenced by chemotherapy drugs. Currently, the chemotherapy drugs on the market can be categorized into the following subtypes: Alkylating agents, antimetabolites, plant alkaloids, and antitumor antibiotics, each with specific working mechanisms. Of all these drugs, platinum-based chemotherapy drugs, one of the alkylating agents, are widely prescribed to treat many types of cancers. However, the platinum-based drug has also shown a relationship with movement disorder. Such is attributed to the neurotoxicity induced by platinum-based chemotherapy drugs.

Motor
As mentioned above, chemotherapy drugs are found to have a correlation with deficits in motor function. The symptoms are oftentimes shown as muscle weakness, muscle mass loss (muscle atrophy), abnormalities in the gait, and difficulties in keeping a balance. The muscle wasting syndrome is also known as cachexia, induced by chemotherapy neurotoxicity. Moreover, the movement disorder often leads to a mental burden on patients, which is usually presented as the fear of falling. Statistics demonstrated that higher fear of falling is related to a high risk of actually falling, which may lead to further injury.

Sensory
Chemotherapy-induced neurotoxicity is not only found in the motor aspect, for example, the movement disorder mentioned, but has also been discovered to affect the sensory aspect. Some of the common symptoms are glove and stocking distal paranesthesia and dysesthesia with loss of tendon reflexes and peripheral sensation, deficits in the vestibular system, and even hearing loss.

In summary, these symptoms developed after cancer and chemotherapy are also known as chemotherapy-induced peripheral neuropathy (CIPN).

Potential Etiology and Pathogenesis
Researchers proposed that cachexia and lots of other neuro-sensory deficits can be attributed to the following mechanisms. First, researchers found out that muscle loss from cancer and chemotherapy is due to the activation of a common signaling pathway leading to mitochondrial function and alternation in the oxidative phosphorylation of the TCA cycle. Secondly, evidence also supports that systematic inflammation after cancer or chemotherapy can elicit the increased secretion of corticosterone, which later binds to the glucocorticoid receptors in the skeletal muscle and induces muscle atrophy. Thirdly, although many researchers consider muscle atrophy to be the cause of movement disorders, further studies reveal that the loss of motor unit connectivity might proceed with the loss of muscle and contribute to the movement disorder. Fourthly, the neurophysiological study found that there was abnormal neurological hyperactivity, which may explain the development of both motor and sensory abnormalities after cancer and chemotherapy.

Treatments
Currently, there is no standard medication treatment for CIPN and cachexia. However, the following research opened up a new gateway either for early diagnosis, potential druggable targets, or physical therapies. First, a wearable device has been designed to detect deficits in motor performance and estimate the progression of CIPN. Enabling the earlier diagnosis can, in turn, give instructions for the amount or time period of further chemotherapy administration. Secondly, researchers proved that stimulation of the soluble guanylate cyclase could inhibit muscle atrophy by promoting protein synthesis and reducing ubiquitin-proteasome pathway activity. Thirdly, it has been proved that sensorimotor training and whole-body vibration training can alleviate the symptoms of CIPN.