New drug could be a game-changer for cancer patients undergoing chemotherapy

New drug could be a game-changer for cancer patients undergoing chemotherapy

Cisplatin is a chemotherapy drug indicated to combat tumors in many types of cancer. However, it has significant side effects – particularly kidney toxicity, which can lead to acute kidney failure. In addition, patients treated with cisplatin also commonly report severe neuropathic pain. Scientists from Inserm, Université de Lille, Lille University Hospital, CNRS and Institut Pasteur de Lille in the CANTHER and Lille Neuroscience & Cognition laboratories, in collaboration with researchers at Michigan State University (USA), have identified a drug that could be a game-changer for patients. Istradefylline, already approved for Parkinson's disease, could not only reduce the harmful effects of cisplatin but also improve its anti-tumor properties. These results now need to be confirmed in a clinical study. The study is published in the Journal of Clinical Investigation.

Cisplatin is a chemotherapy drug used to treat various types of cancer, particularly lung, ovarian and testicular cancer. While its anti-tumor effectiveness has been proven, cisplatin promotes side effects. These include severe pain (peripheral neuropathy) and kidney damage, which leads to acute kidney failure in a third of cases. There are currently no effective solutions to limit side effects in patients exposed to cisplatin.

An international work led by Christelle Cauffiez, David Blum and Geoffroy Laumet has now identified a molecule that reduces cisplatin-induced side effects while maintaining or even enhancing its anti-tumor properties.

A drug for Parkinson's disease

The scientists focused on a drug called istradefylline, which is already approved in the United States and Japan to treat Parkinson's disease. Biologically, this compound blocks the adenosine receptors on the surface of cells.

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Blum's team, which studies neurodegenerative diseases, had previously observed an increased density of these receptors in the brains of patients with dementia, a phenomenon that is involved in the development of these diseases. Interestingly, Cauffiez's team observed a similar increase in adenosine receptors in the kidneys under cisplatin exposure.

With this in mind, the scientists decided to team up with the laboratory of Laumet, a specialist in cisplatin-induced neuropathic pain, to test the effect of istradefylline in attenuating the harmful effects of cisplatin.

Confirm results in a clinical study

Their experiments, conducted on animal and cell models, actually suggested a beneficial role for istradefylline. In mice exposed to cisplatin, the molecule not only reduced kidney damage but also prevented neuropathic pain.

In addition, cisplatin's ability to reduce tumor growth was increased in the animals that received istradefylline - an effect that was later confirmed in cell models.

However, before considering the widespread application of this therapeutic approach in cancer patients, these results must first be consolidated through the organization of a rigorous clinical trial. The fact that istradefylline is already being used in humans to treat another disease is an interesting prospect.

"In fact, we already have a lot of clinical data showing that this molecule is safe. While it is necessary to conduct a clinical trial to test its effectiveness in reducing the side effects of chemotherapy, the possibility of therapeutic repositioning is a promising prospect to improve patient care in the short term," emphasize the researchers.

Source:

INSERM (National Institute for Health and Medical Research)

Reference:

Dewaeles, E., et al. (2022) Istradefylline protects against cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving the antitumor effects of cisplatin. Journal of Clinical Investigation. doi.org/10.1172/JCI152924.

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