Preclinical Models of Anal Cancer Combined-Modality Therapy

• Published in: The Journal of surgical research Vol. 294; pp. 82 - 92
• Main Authors: Johnson, Hillary R, Gunder, Laura C, Gillette, Amani, Sleiman, Hana, Rademacher, Brooks L, Meske, Louise M, Culberson, Wesley S, Micka, John A, Favreau, Peter, Yao, Evan, Matkowskyj, Kristina A, Skala, Melissa C, Carchman, Evie H
• Format: Journal Article
• Language: English
• Published: United States 01.02.2024
• Subjects: Anal Canal - pathology; Animals; Anus Neoplasms - pathology; Anus Neoplasms - therapy; Carcinoma, Squamous Cell - pathology; Combined Modality Therapy; Mice; Mice, Transgenic; mTOR; Pik3ca; PI3K; Cancer treatment; Chemoradiotherapy; Anal cancer
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2023.09.053

There have been no significant changes in anal cancer treatment options in 4 decades. In this study, we highlight two preclinical models designed to assess anal cancer treatments. Transgenic K14E6/E7 mice were treated with 7, 12-dimethylbenz(a)anthracene until anal tumors developed. Mice were treated with localized radiation in addition to chemotherapy (combined-modality therapy [CMT]) and compared to no treatment control (NTC). K14E6/E7 mouse anal spheroids with and without Pik3ca mutations were isolated and treated with vehicle, LY3023414 (LY3) (a drug previously shown to be effective in cancer prevention), CMT, or CMT + LY3. In the in vivo model, there was a significant increase in survival in the CMT group compared to the NTC group (P = 0.0392). In the ex vivo model, there was a significant decrease in the mean diameter of CMT and CMT + LY3-treated spheroids compared to vehicle (P ≤ 0.0001). For LY3 alone compared to vehicle, there was a statistically significant decrease in spheroid size in the K14E6/E7 group without mutation (P = 0.0004). We have provided proof of concept for two preclinical anal cancer treatment models that allow for the future testing of novel therapies for anal cancer.