Abstract 5950: A novel biguanide as a potential head and neck cancer therapeutic in Fanconi anemia

Abstract Introduction: Fanconi Anemia (FA) patients develop head and neck squamous cell carcinoma (HNSCC) at significantly elevated rates and conventional adjunctive chemotherapy and radiation are exquisitely toxic to these patients. We endeavor to find a safer chemotherapeutic agent for treatment of head and neck cancer in this population. Currently, agents such as metformin are in FA clinical trials for marrow failure and are also high interest agents in head and neck cancer chemoprevention. HNSCC in FA is a disease model that has applications to typical head and neck cancer, as its mutational defects are felt to be similar. Methods: We completed cell proliferation assays on FA-derived HNSCC cell lines MOP FA-1 and VU-1131. MTT, Cell Titer Glo, trypan blue, and clonogenic assays were completed on each cell line to evaluate the effect of N1-hexyl-N5-benzyl-biguanide (HBB) in comparison with standard cisplatin chemotherapy. We also compared the caspase activity in an effort to evaluate a putative mechanism of HBB cellular inhibition. Results: HBB showed a statistically significant dose-dependent inhibition of cellular proliferation. In MTT assays, 5 uM HBB showed 28-46% inhibition at 72 hours and 10uM HBB showed 77-82% inhibition at 72 hours. There was an additive inhibition of cellular proliferation when HBB was combined with low-dose cisplatin. Conclusion: HBB is a novel biguanide that inhibited cellular proliferation in two FA HNSCC cell lines and chemosensitized to low-dose cisplatin. This may be an alternative adjunct treatment agent, or may be chemosensitizing for low-dose cytotoxic agents such as platinum-based chemotherapeutics in this unique population. Citation Format: Hunter Archibald, Beverly Wuertz, Frank Ondrey. A novel biguanide as a potential head and neck cancer therapeutic in Fanconi anemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5950.