Tumor growth, prediction

While the obvious value of in vivo animal models is clear, there also are instances—especially in cases of inflammatory arthritis, behavior, and tumor growth—where they have failed to be predictive of useful clinical activity in humans [51], For example, leukotriene (LTB4) antagonists showed activity in animal models of inflammatory arthritis yet failed to be useful in rheumatoid arthritis [52]. Similarly, dopamine D4 antagonists showed activity in animal behavior models previously predictive of dopamine D2 antagonists in schizophrenia. However, testing of dopamine D4 antagonists showed no efficacy in humans [53]. 

Formation of regional lymph node metastasis can be an important step in dissemination of cancer cells. In colorectal cancer, lymph node metastasis frequently occurs in patients (7, 8) and is an important factor in staging the disease. In particular, the metastatic lymph node ratio (LNR number of metastatic lymph nodes/number of examined lymph nodes) is predictive of overall survival (OS) and disease-free survival (DFS) in colorectal cancer patients (9, 10). Hence, an animal model of colorectal cancer with measurable lymphatic metastasis that allows for rapid evaluation of the effects of candidate treatment regimens on primary tumor growth and lymph node metastasis would be of great value. 

The predictions of this simple model agree surprisingly well with data on tumor growth, as long as N is not too small see Aroesty et al. (1973) and Newton (1980) for examples. 

Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 64 1094-1101 (2004). 

As mentioned above, drug potency is a body weight independent parameter, and it should be the same across species. Therefore, Vk2 obtained from a mouse model can be used to predict the total AUC during the mean tumor growth time in humans. It was demonstrated that Vk2 obtained from human tumor xenografts in nude mice correlates to total AUC in a three-week cycle in human for 10 anticancer agents at their average therapeutic dose [55],... 

Fxmctional models were later generated to predict tumor growth in terms of cell kinetics and/or cell-cell interactions. More importantly, these models allow for the incorporation of growth inhibition and stimulation by autocrine (tumor-derived), paracrine (microenvironment), or humoral/exogenous mediators. While the mathematical derivation of these relationships is beyond the scope of this chapter, it clearly represents an effort to model receptor-mediated processes, auto-stimulation, negative and positive feedback loops, and dynamic processes between competing subpopulations of... 

Head, J. F., Wang, F., and Elliott R. L., 1993, Breast Thermography Is a Noninvasive Prognostic Procedure That Predicts Tumor Growth Rate in Breast Cancer Patients, Ann. New York Acad. Sci., 698 153-158. 

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