Abstract 49: Comparison of subcutaneous and orthotopic tumor growth in syngeneic mouse models of ovarian and renal cancer

Abstract Oncology drug development has markedly lower success rate (3.4%) than other indications (20.9%) as reported by Wong, Siah and Lo in 2019. Animal models are often pointed at as the culprits for failure in clinical trials. While better animal models for cancer are needed and constantly developed, the incentive of drug developers to use those might not be clear, because the regulatory authorities do not require it. Subcutaneous tumors have earned their place in drug development but adding more sophisticated models to the testing panel before entering the clinical phase should improve the success rate. We present here the properties of subcutaneous and orthotopic tumor growth in two syngeneic models. HM-1 murine ovarian cancer cells were inoculated subcutaneously (s.c.) and intraperitoneally (representing the stage of intraperitoneal carcinomatosis) and murine renal adenocarcinoma Renca cells s.c. and orthotopically within the renal capsule. Body weight and tumor growth were followed, and mice were sacrificed according to humane endpoint criteria. To compare tumor growth in s.c. sites and within the abdomen, the tumor weight at sacrifice was divided by the number of days since the inoculation. In the HM-1 model, the mice with intraperitoneal tumor were sacrificed due to build-up of ascites on average six days earlier that the mice with s.c. tumor. In s.c. HM-1 tumor-bearing mice, the reason for sacrifice was tumor ulceration. In the Renca model, the s.c. and intrabursal models were approximately the same length. There was a striking difference in the tumor growth rate (mg/day) in s.c. versus abdominal sites in both models. The growth was 4-5 times faster in the abdominal sites than subcutaneously, highlighting the effect of tumor specific microenvironment. It is easy to understand that having promising results might be easier in a slower growing model. However, since both ovarian and renal cancer show very different growth kinetics within the abdominal cavity, testing drug candidates aimed for those indications in orthotopic models before accessing the clinical trials could give a more relevant evaluation of the potency of the drug candidates. Citation Format: Mari I. Suominen, Justyna Zdrojewska, Yvonne Konkol, Katja M. Fagerlund, Mervi Ristola, Jukka P. Rissanen. Comparison of subcutaneous and orthotopic tumor growth in syngeneic mouse models of ovarian and renal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 49.