Abstract 4767: Changes in the NSE and S100B levels following treatment with peripheral neuropathy-inducing drugs

Abstract

Abstract Neo-adjuvant chemotherapy is considered the standard of care for patients with multiple myeloma (MM). Peripheral neuropathy (PN) is one of the most common chemotherapy-induced side effects that impact 50% of all patients who receive chemotherapy and can lead to discontinuation of drug treatment. Treatment with Bortezomib (BTZ), Cisplatin (CIS), and Vincristine (VIN) has been established as the most common trigger of Chemotherapylnduced Peripheral Neuropathy (CIPN) among cancer patients. Since CIPN can lead to disabling long-term adverse effects, many cancer patients discontinue or limit their treatment regimen once they see signs or symptoms of CIPN. Therefore, it was hypothesized that developing diagnostic/prognostic biomarkers that can accurately predict the onset or progression of CIPN would help to determine the chemotherapy eligibility with the above-mentioned drugs and proactively prepare for protective care. Hence, our initial goal was to elucidate the molecular mechanisms underlying the onset and progression of CIPN that would allow for the identification of suitable biomarkers that can be used for monitoring before or during chemotherapy with BTZ, CIS, and VIN. Initially, we conducted in vitro studies to identify the underlying molecular mechanisms activating CIPN related pathways. We used neuronal Schwann cells (RT4), for testing the neurotoxic effects of BTZ, CIS, and VIN that might precede or coincide with the onset of CIPN in an in vivo condition. Interestingly, the BTZ treatment was able to significantly reduce the intracellular level of NSE and S100B in RT4 cells compared to the untreated controls, when they were measured using an immunofluorescence assay and Western blot. Furthermore, we conducted an in vivo study to determine the CIPN using rats. We used the sciatic nerve (SN) from drug-treated animals to check the S100B level using the ELISA method. Our preliminary results showed that levels of S100B in the SN of Rats were reduced following 8 weeks of treatment with the PN-inducing chemo drugs. We anticipate that this study will enrich our understanding of how chemotherapy medications induce PN in cancer patients and guide us to identify reliable biomarkers (This project was supported by the PFRDG grant of the Nova Southeastern University, Ft. Lauderdale Florida, and the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida). Citation Format: Priya R. Vontikommu, Shriya Selvakumar, Umamaheshwari Natarajan, Appu Rathinavelu. Changes in the NSE and S100B levels following treatment with peripheral neuropathy-inducing drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4767.