Relieving the side effects of chemotherapy

Every two weeks, a current scientific topic is explored by a researcher from the Collège de France.

Necessary in the fight against cancer, chemotherapy causes numerous side effects. One of these, peripheral neuropathy, is characterized by acute pain in the extremities of the limbs. However, by studying the interaction between neurological and vascular systems, we may be able to alleviate these side effects and pave the way for new medical approaches.
Interview with Isabelle ^Brunet*, biology researcher at the Collège de France.

Oxaliplatin is a chemotherapy mainly used in the fight against digestive cancers. In almost 80 % of patients, this treatment leads to acute peripheral neuropathy, causing severe pain in the hands and feet. This pathology affects the peripheral nervous system that innervates organs and limbs, causing tingling and burning sensations for which there is no specific solution.

Until now, research has focused on understanding how nerve endings function. However, recent studies show that the problem stems from interaction with the blood vessels that supply the nerves. For researcher Isabelle Brunet, this relationship is crucial :" We want to understand how blood vessels and nerves influence each other, in normal and pathological contexts. "

Having long evolved independently, neuroscience and cardiovascular biology are now focusing on how neurological and vascular systems communicate, and their roles in pathology. In the context of peripheral neuropathies, this approach is particularly relevant.

Preventing neuropathies

The study of chemically-induced peripheral neuropathies reveals the critical role played by blood vessels in the onset of these pains. Unexpectedly, there is no damage to the vessels themselves, but their ability to contract is disrupted. Isabelle Brunet explains :" We observe that blood vessels, in response to oxaliplatin, contract more than they should, reducing blood flow to the nerves. " The nervous system is made up of tissues that are highly demanding in terms of oxygen and nutrients supplied by the blood. The reduced blood flow caused by vessel contraction mechanically reduces these supplies.
This discovery offers immense hope, as the only treatments currently prescribed to relieve this crippling pain are opioids, which give rise to dependency problems. Prescribing drugs to avoid this contraction reduces the symptoms of the disease, and prevents them from appearing in the first place.

Despite its novelty, this approach could rapidly become available to patients, using generic drugs already on the market. For the researcher, however, it remains to be ensured that these treatments do not affect the efficacy of chemotherapies. Isabelle Brunet is working with oncologists and neurologists to test this hypothesis :" We need to prove that these drugs, while preserving the nerves, do not interfere with the efficacy of chemotherapy. "

Transdisciplinary research

The avenues opened up by this research are not limited to peripheral neuropathies. They open the way to a better understanding of many neurological and vascular pathologies. In diseases such as Alzheimer's, or cerebral edema, this interface could reveal as yet unsuspected mechanisms. The researcher emphasizes :" We have decided to focus on pathologies where there is a therapeutic impasse. " The challenge for the future lies in exploring this nerve vascularization and its role in various more common pathologies, such as carpal tunnel syndrome. These pathologies, although sometimes less serious, affect a large number of people and lead to chronic pain that is often poorly managed. Isabelle's aim is to develop innovative solutions based on a better understanding of the mechanisms involved.

To achieve this ambitious goal, Isabelle Brunet and her team have launched a European project. The aim of this initiative is to study the plasticity of nerve vessels and their ability to protect nerves against mechanical and pathological stress. Given the constant stresses to which nerves are subjected in the body, " understanding how blood vessels support them could revolutionize their management, not only in severe cases, but also in more common, but equally disabling disorders ", she explains.

Studying the interface between the nervous and vascular systems not only solves a medical problem, it also offers tangible hope to thousands of patients suffering from peripheral neuropathies and other painful pathologies.

*Isabelle Brunet is head of the Molecular Control of Neurovascular Development team at the Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France.