Targeted strategy prevents untreatable nerve pain caused by chemotherapy

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New research out of VCU Massey Comprehensive Cancer Center—published in Brain, Behavior and Immunity—is the first to suggest that a tumor-driving gene known as AEG-1 actively regulates the inflammation responsible for causing chemotherapy-induced peripheral neuropathy (CIPN), a common and painful side effect of cancer treatment. Eliminating the function of this gene using targeted therapies could become a critical strategy for managing a debilitating side effect experienced by many cancer patients.

“Currently, there are no FDA-approved medications designed to specifically treat or prevent chemotherapy-induced peripheral neuropathy in cancer patients, and the current clinical approach for the management of it is inadequate,” said study author M Imad Damaj PhD, member of the Cancer Prevention and Control research program at Massey and a professor in the Department of Pharmacology and Toxicology at the VCU School of Medicine. “Our findings could help pave the way for the development of an entirely new and effective therapeutic option for chemotherapy-induced peripheral neuropathy.”

Previous research from Damaj and other scientific groups has shown that chemotherapy drugs cause universal inflammation throughout the body, significantly damaging a patient’s nerve endings. This is one of the main contributors to the pain associated with chemotherapy-induced peripheral neuropathy.

Common symptoms of chemotherapy-induced peripheral neuropathy include pain, tingling, numbness, or sensitivity in the hands or feet caused by damage to the nervous system. The presence of chemotherapy-induced peripheral neuropathy can often reduce a cancer patient’s manageable treatment dose and, if the pain is too severe, the chemotherapy regimen might be stopped altogether, forcing an oncologist to prescribe a less effective but more tolerable drug for their patients.

Platinum-based drugs and taxanes —two classes of chemotherapy drugs—are most routinely culpable in the onset of peripheral neuropathy in cancer patients. The majority of patients will recover within a couple of months from the symptoms of chemotherapy-induced peripheral neuropathy; however, a large percentage—approximately 25-30%—will experience chronic neuropathy. To alleviate these side effects, patients with chemotherapy-induced peripheral neuropathy may often be prescribed opioids, highly addictive pain medications.

“One of the major advantages supported by our findings is that we’ve identified a promising strategy through which we can pursue new targeted treatments as an alternative to more addictive pain medications,” said study co-author Devanand Sarkar MBBS PhD, the associate director for research training and education who holds the Harrison Foundation Distinguished Professorship in Cancer Research at Massey, as well as a professor of cellular, molecular and genetic medicine at the VCU School of Medicine.

AEG-1 is a known oncogene, playing a central role in inflammation and driving tumor growth. Sarkar has been studying the biological function of AEG-1 and its relationship to inflammation for more than two decades, primarily in the development of fatty liver disease and liver cancer. Previous research findings have directly implicated AEG-1 and inflammation in cancer progression and drug resistance; however, no studies have previously investigated the role of AEG-1 as it directly relates to the development of chemotherapy-induced peripheral neuropathy.

Using preclinical models, the research team deleted the presence of AEG-1 in myeloid cells—a family of immune cells that plays a role in the development of tumors—effectively inhibiting the neuroinflammation brought on by chemotherapy, and overall preventing the onset of chemotherapy-induced peripheral neuropathy.

“Our work demonstrates that targeted inhibition of AEG-1 in myeloid cells may represent a novel therapeutic approach to preventing chemotherapy-induced peripheral neuropathy, which in turn could improve treatment adherence and the quality of care for cancer patients receiving taxanes or platinum-based drugs,” said study co-author Bryan McKiver MS PhD, a postdoctoral associate in therapeutic radiology at Yale University, who was a PhD student at the VCU School of Medicine while conducting this research.

Additionally, the study authors believe that targeting AEG-1 in macrophages—a type of white blood cell found within tumors—could have the bonus effect of reducing tumor size while simultaneously preventing chemotherapy-induced peripheral neuropathy.

“If effective, this double weapon approach may represent a holistic therapeutic strategy that can be utilized to prevent both cancer progression and chemotoxicity, which could drastically improve survivorship and quality of life for patients diagnosed with cancer,” Damaj said.

Looking ahead, the research team hopes to build upon these findings by further evaluating the efficacy of different targeted treatments for the prevention of chemotherapy-induced peripheral neuropathy through clinical trials. Further research will need to be conducted to determine if this treatment strategy can reverse the effects of established chemotherapy-induced peripheral neuropathy in patients.

Source: News Release
Virginia Commonwealth University
June 28, 2025