George Mason University and VCU partnership seeks answers to chronic neuropathy pain after breast cancer treatment

A new research collaboration between George Mason University and Virginia Commonwealth University (VCU) aims to improve understanding of peripheral neuropathy, a painful and often life-altering side effect experienced by breast cancer survivors involving damage to the nerves that can interrupt daily function.

With a $200,000 grant from the Commonwealth Health Research Board, the project, "Proteomic and Neuroimmune Signatures of Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer," focuses on chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of chemotherapy that affects more than 50% of patients, with up to 30% experiencing persistent symptoms that can interfere with treatment and become chronic.

Lead by Nadine Kabbani, a professor in George Mason's Interdisciplinary Program in Neuroscience; Imad Damaj of VCU's Department of Pharmacology and Toxicology; and Paula Bos of the VCU Massey Comprehensive Cancer Center, the project brings together expertise in neuroscience, cancer biology, pharmacology, proteomics, and artificial intelligence.

Damaj is a highly accomplished investigator with extensive expertise in neuropathic pain, including CIPN. Bos brings deep expertise in breast cancer biology and has been instrumental in establishing the team's clinically relevant breast cancer model of CIPN. Together, the investigators provide complementary expertise, with Kabbani leading the proteomics, neuroimmune, and computational systems biology components of the project.

"Bringing a cancer biologist into the neuropathy research space has helped us think about the problem differently," Kabbani said. "The side effects of any treatment occur within a specific context. We believe understanding that context may change the way the field approaches neuropathy."

The findings could have broad implications for cancer survivors, clinicians, and researchers working to reduce long-term treatment-related complications.

"Cancer survival rates have improved dramatically, especially for breast cancer," said Kabbani, a George Mason alumna and neuroscientist whose research focuses on molecular neuroscience, immune signaling, and public health. "But many survivors continue to live with neuropathy long after their cancer treatment ends. Understanding why that happens is critical if we want to improve quality of life after cancer."

What makes the project distinctive is its focus on the cancer itself-not just the chemotherapy. Historically, many studies have treated chemotherapy as the sole driver of neuropathy. Kabbani and her collaborators theorize that the biological environment created by cancer may also contribute to pain development.

"The prevailing view has been that chemotherapy damages nerves and that damage causes pain," Kabbani explained. "Our work suggests that the cancer background matters too. The cancer changes the immune environment, and that may influence how neuropathy develops."

The team has developed a breast cancer model that more accurately reflects the conditions experienced by patients. Researchers will use the model to examine how both cancer and chemotherapy reshape sensory pathways involved in pain perception.

"We're interested in how the nervous system rewires itself," said Kabbani. "Chronic pain isn't simply a response to an injury. It reflects long-term changes in how information is processed. We want to understand the molecular networks that drive those changes."

In addition to generating new scientific knowledge, the award provides valuable research opportunities for graduate students and early-career scientists at both institutions.

George Mason biosciences PhD student Samantha Schwarting, the leading graduate student on the study, has been working with Christopher Lockhart, an assistant professor in George Mason's School of Systems Biology, developing computational approaches to analyze the project's large-scale datasets.

After taking a machine learning course with Lockhart, Schwarting began applying her newly learned knowledge to develop a new graph of neural networks, a form of artificial intelligence (AI), for analyzing her proteomic data. This AI model now allows Schwarting and the team to evaluate how thousands of proteins interact within complex biological networks rather than focusing only on just individual proteins showing the largest changes as typically done.

Schwarting's graduate research assistantship is being funded by George Mason's Grand Challenge Initiative-sponsored Quantum Leap project, which champions applying quantum computing to complex biological problems.

"Machine learning allows us to identify the influential players within a complex system," Schwarting explained. "Sometimes the proteins driving the network aren't the ones changing the most. AI helps us find relationships we might otherwise miss."

Those insights could ultimately support the development of more targeted therapies and accelerate efforts to repurpose existing drugs for neuropathy treatment.

"More people are surviving cancer than ever before," Kabbani said. "That means we need to put equal energy into helping survivors live well after treatment. Understanding the biology of chronic neuropathy is an important step toward that goal."