Abstract LB173: Growth kinetics of Fanconi anemia derived head and neck cancer cells <i>in vitro</i> and <i>in vivo</i>

Abstract Introduction: Treatment of head and neck cancer in Fanconi anemia (FA) patients is highly challenging because all conventional chemo radiotherapy exacerbates DNA damage which is deleterious in these patients. We have been working with Wee kinase cell cycle inhibitors in vitro to potentially treat these cancers and avoid DNA damage. In the current study we sought to establish growth kinetics of Fanconi anemia and non FA squamous cancer cells to compare with human head and neck cancer growth rates. We hypothesized that if we observed preclinical experimental cellular growth rates to actual human head and neck cancer growth, a more accurate cancer treatment model would be achieved. Methods: We first examined the growth kinetics of several FA/ non FA cell lines in MTT assays and nude mice xenografts. We next compared these pre clinical growth kinetics to the human head and neck cancer tumor literature and clinical data. P&amp;lt;0.05 was significant. Results: For the FA tumor cell lines we found growth rates ranging from 4-220% /day on MTT Assays. For non FA tumor cell lines we found growth rates ranging from 31.2 -53.0 %/day on MTT assays. For the FA tumor cell lines we found growth rates ranging from 0.7- 23.2%/day in mouse xenografts. For HeLa cells (a non FA tumor squamous cell line) we found growth rates ranging from 10.7 - 24.5%/day in mouse xenografts. In the human tumor literature and rapid growing clinical specimens we found growth rates from 0.1%- 15.1% / day. We found a wide variety of growth kinetics in head neck cancer cell lines of FA and non FA patients that were not significantly different from each other in standard MTT experiments. Some experimental conditions in setting up mouse xenograft experiments with FA cell lines, (but not HeLa xenografts) more closely resembled published human tumor growth rates (0.1-4.2%/day). In general, growth rates were all more rapid in cell line and animal xenograft experiments than human head and neck cancer clinical tumors. Conclusions: We discovered effects of cell cycle disruptors like Wee kinase inhibitors are likely to show significantly amplified effects in preclinical experiments compared to actual human squamous tumor treatment. Therefore, there might be improved utility in carefully designing preclinical experiments with cell cycle disrupting therapy (like WEE kinase inhibitors) to resemble human tumor kinetics. Citation Format: Nathan DeMichaelis, Sanjana Arji, Haley Ring, Beverly Wuertz, Frank G. Ondrey. Growth kinetics of Fanconi anemia derived head and neck cancer cells in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB173.