Cancer animal models

In addition to in vivo studies in models of CML, BMS-354825 has also been studied in models of solid tumors. BMS-354825 was efficacious in head and neck squamous cell carcinoma and non-small cell lung cancer animal models [151]. Based on this activity, BMS-354825 has been advanced into clinical trials for the treatment of solid tumors. 

Morroquin et al. [44] studied the effect of high-dose IL-2 therapy in the treatment of patients with metastatic melanoma and renal cell cancer. Animal models have shown that successful treatment with IL-2 is dose and schedule dependent. They found that there was a subset of patients who could not tolerate high doses or retreatment due to renal toxicity. Pretreatment factors that were significantly associated with renal toxicity were male sex, diagnosis of renal cancer, previous nephrectomy, and older age. These patients also had higher baseline creatinine. 

Kawakami, K., Kawakami, M., and Puri, R.K. (2004). Nitric oxide accelerates interleukin-13 cy totoxin-mediated regression in head and neck cancer animal model. Clin. Cancer Res. 70(15), 5264-5270. 

Toxicity Amelioration. Cancer researchers traditionally have not focused their attention on the question of toxicity amehoration. This is partiy attributed to the lack of predictive animal models for human toxicities. For example, the preclinical rat model, used as a predictor of myelosuppression, has failed to predict myelosuppression in humans in clinical trials. In addition, reduction of one toxicity may result in the emergence of another, more serious problem. Research efforts to address the problem of toxicity amelioration has progressed in several directions. The three most prominent areas are analogue synthesis, chemoprotection, and dmg targeting. 

Increased production of ROMs has been demonstrated by an animal model of colorectal cancer (McKeever etal.,... 

In recent decades, the development of chemical, biochemical, and biological techniques has allowed the creation of analytical tools which can be used to facilitate the identification of the mechanisms involved in neoplastic transformation. Animal models remain, however, the most widely used approach of investigation. Cancer bioassays are usually conducted in rodents (rats and mice) and the experimental protocol takes 18-24 months and it is followed by extensive histopathological and statistical analysis. The procedure is time and... 

Duke University bioengineers have developed a simple and inexpensive method for loading cancer drug payloads into nanoscale delivery vehicles, and have demonstrated in animal models that this new nanoformulation can eliminate tumors after a single treatment [109]. After delivering the drug to the tumor, the delivery... 

Kukowska-Latallo, J.F., Candido, K.A., Cao, Z., Nigavekar, S.S., Majoros, I.J., Thomas, T.P., Balogh, L.P., Khan, M.K., and Baker Jr., J.R. (2005) Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res. 65(12), 5317-5324. 

Boone CW, Kelloff GJ and Maolone WE. 1990. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials a review. Cancer Res 50 2-9. 

Experiments conducted in the early 1980s showed that lymphocytes incubated in vitro with IL-2 could subsequently kill a range of cultured cancer cell lines, including melanoma and colon cancer cells. These latter cancers do not respond well to conventional therapies. Subsequent investigations showed that cancer cell destruction was mediated by IL-2-stimulated NK cells (i.e. LAK cells). Similar responses were seen in animal models upon administration of LAK cells activated in vitro using IL-2. 

Experimental studies showed antitumoral effects of raloxifene in different in vitro preparations and animal models. Raloxifene has been able to inhibit the mitogenic effect induced by estrogens on ZR-75-1 cells, an estrogen responsive human breast cancer cell line (Poulin et al. 1989). In a well-accepted rat model of breast cancer induced by nitroso-methyl urea (NMU) raloxifene significantly suppressed the development of breast tumors and acted synergistically with 9 cis-retinoic acid (Anzano et al. 1996). 

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