Integrating nutrition and proteomics to improve chemotherapy-induced peripheral neuropathy in cancer survivors

/ABSTRACT Platinum-based chemotherapy is the standard of care for several cancers; however, chemotherapy-induced peripheral neuropathy (CIPN) results in lower quality of life and chemotherapy dose reductions that reduce survival. Platinum-based chemotherapies induce DNA damage to neuronal cells. Increases in pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), decreases in anti-inflammatory cytokines (IL-10, IL-4), and increased oxidative stress alters neuronal excitability, resulting in tingling, pain, and changes to physical function associated with CIPN. DNA damage also impacts proteins released from cells and downstream cellular regulation reflected in the proteome, representing an opportunity to identify biological mechanisms of CIPN. We have shown that higher dietary quality is associated with reduced incidence of CIPN. However, the Pathways to Prevention (P2P) workshop, co-sponsored by five institutes and offices of the National Institutes of Health, identified a lack of high-quality data on whole diet interventions to manage chemotherapy side effects across cancer types. Characterizing the association between diet and CIPN across multiple cancers, while leveraging methods that capture mechanisms that mediate this relationship, will facilitate clinical nutrition guidelines to improve chemotherapy tolerability and survival. Our overall hypothesis is that diet may impact the development of CIPN by reducing inflammation and oxidative stress as reflected in the proteome in patients receiving platinum-based chemotherapies. Leveraging the NCI-sponsored Exercise and Nutrition Interventions to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium, we will determine the relationship between diet and CIPN incidence across multiple cancer types (Aim 1) and create a testable assay of CIPN mechanisms using proteomics (Aim 2). Completion of these aims will inform the conduct of a randomized trial using a dietary intervention to delay CIPN, improve inflammation and antioxidant biomarkers, and prevent reductions in physical functioning (Aim 3). This is coupled with a robust career development plan that incorporates didactic coursework, hands-on application, and benchmarks for success to provide the applicant with (1) knowledge in oncology practice and standard of care treatment, (2) expertise in conducting rigorous nutrition interventions in oncology, (3) integration and interpretation of omics and high- throughput data into behavioral clinical trials, and (4) scientific leadership, team management, and mentorship skills to become a successful independent investigator. Combined with a world-class mentoring team and strong institutional support at Pennington Biomedical Research Center, this Pathway to Independence Award provides specialized training that optimally positions the applicant towards her career goal of transforming nutrition care in oncology. This research answers the call to action put forth by the P2P workshop and advances research priority missions of the NCI for cancer survivorship and cancer control. Project Number: 1K99CA308896-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Stephanie Compton | Institution: ADVENTHEALTH ORLANDO, ORLANDO, FL | Award Amount: $176,256 | Activity Code: K99 | Study Section: Special Emphasis Panel[ZRG1 CDPT-N (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11292989