Chemotherapies, drugs used to fight cancer by killing tumor cells or preventing them from growing and dividing, remain some of the most common cancer treatments. Chemotherapy regimens differ based on several factors, including the type and stage of cancer and the patient’s general health and comorbidities. Sometimes chemotherapy may be administered alone, but in some cases, doctors combine it with other treatments like surgery or radiation.
While chemotherapy can effectively eliminate cancer, even responsive patients may experience severe side effects. The toxicities occur because chemotherapy does not discriminate- it kills cancer cells and healthy cells. Because most chemotherapy drugs target fast-growing cancer cells, it also continues to be highly efficient in killing fast-growing healthy cells, like those in the mouth and intestines, common sites of chemotherapy-associated side effects. Hair roots, which contain the cells responsible for hair growth, are another common target of chemotherapy leading to hair loss often associated with this kind of therapy.
Cisplatin is a standard chemotherapy approved to treat bladder, ovarian, and testicular cancers. In addition, clinical trials to test the efficacy of cisplatin in treating several other types of cancer, including lung, head and neck, brain, and colorectal cancers, are ongoing. Major complications associated with cisplatin involve the kidneys (nephrotoxicity) and the nerves (peripheral neuropathy). Both nephrotoxicity, which can result in kidney failure, and peripheral neuropathy, which causes severe pain and numbness in the hands and feet, can become debilitating and may even lead a patient to discontinue a life-saving treatment. Thus, strategies that reduce cisplatin's side effects while maintaining the anti-cancer effects are necessary to support cancer patients who can benefit from this treatment.
One research team investigating ways to augment cisplatin-associated toxicity recently published findings in the Journal of Clinical Investigation. The study demonstrates that istradefylline, a drug used to treat Parkinson’s disease, protected tumor-bearing mice from cisplatin-induced nephrotoxicity and neuropathy. Not only does istradefylline reduce the adverse effects associated with cisplatin, but it also preserves the cancer-killing properties of the chemotherapy.
Istradefylline works by binding a receptor on adenosine, a molecule that plays an integral role in the health of cells and tissues throughout the body. The current study suggests that, in mouse models, istradefylline protects from nephrotoxicity, in part, by limiting the accumulation of platinum, the element which makes up cisplatin, in the kidneys. Additionally, the istradefylline-treated mouse models used in this study also experienced less cisplatin-induced pain. The researchers found the reduction in cisplatin-induced pain occurred because istradefylline limited the expression of inflammatory cytokines, proteins that can impair the immune system.
These findings suggest that istradefylline could be repurposed as a preventive approach for patients receiving cisplatin treatment. Because istradefylline is already considered safe, it could facilitate rapid translation to clinical applications following successful clinical trials.
Sources: Natl Library Med, Toxins, Ann Neurol, J Clin Invest, Purinergic Signal