Abstract
As preclinical chemotherapists, we are often asked to identify experimental tumor models that can accurately predict for the drug response characteristics of all tumors of a given cellular subtype or molecular target. Unfortunately, it is impossible to give satisfactory answers to these inquiries. Because of the unique character of each independently arising tumor (whether spontaneous or induced), it does not take very long to realize that each tumor is a unique biologic entity with its own tumor growth behavior, histological appearance, drug response and molecular expression profiles. This is true whether the tumor is an experimental animal model or one originally derived from a patient. Further, many factors can influence the tumor growth and therapy response of experimental tumor models. Still, in vivo models are needed to adequately assess pharmacodynamics, toxicity and efficacy of any potential novel therapy. Presented herein is what we hope will be useful information regarding the transplant characteristics of tumor models, with some of the “pitfalls” to look out for when using any given tumor model for chemotherapy evaluations. Although most of the examples given use syngeneic models, the methodologies for assessing the predictive worth and maintaining model usefulness can be applied to almost any given transplantable tumor system (whether syngeneic or xenograft).
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- 1.
There is a relationship between tumor size and cell number. With syngeneic, transplanted mouse tumors, the tumor mass is usually >85% tumor cells while in exponential growth. A 1 g mass (1,000 mg) = 1 × 109 cells; a 0.1 g mass (100 mg) = 1 × 108 cells; a 0.01 g mass (10 mg) = 1 × 107 cells; a 1 mg mass = 1 × 106 cells, and so on. Thus, a 30 mg mass = 3 × 107 cells (30 million cells). Human tumor cells and mouse tumor cells are approximately the same size, but only a few xenografted human tumors contain >80% tumor cells. Td = exponential tumor-volume doubling time. 3.32 = number of doublings per log. Cure is usually obtained when the population is reduced to approximately 10 or 100 cells for most solid tumors.
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Acknowledgments
This work was supported by CA12623, CA82341, CA53001, Sanofi-Aventis previously Sanofi Synthelabo Research, and Eli Lilly Corporation.
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Polin, L. et al. (2011). Transplantable Syngeneic Rodent Tumors: Solid Tumors in Mice. In: Teicher, B. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-968-0_3
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