Tumor Models in Cancer Research
Beverly A. Teicher and a panel of leading experts comprehensively describe the state-of-the-art in animal tumor model research. This volume updates and extends the comprehensive presentations in the first edition. The wide array of models detailed form th
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Preclinical Tumor Response End Points Beverly A. Teicher
Abstract The first in vivo tumor models were developed in the mid-1960s. These models were mouse leukemia models grown as ascites. The growth pattern was like that of bacteria in vivo and therefore it was possible to apply similar mathematics of growth and response to these tumors as had been worked out for bacteria. Since the development of the murine leukemia models, investigators have devoted a large effort to modeling solid tumors in mice. There are now a variety of models including syngeneic mouse tumors and human tumor xenografts grown as subcutaneous nodules, syngeneic mouse tumors and human tumor xenografts grown in orthotopic sites, models of disseminated disease, ‘‘labeled’’ tumor models that can be visualized using varied technologies, and transgenic tumor models. The value of these models depends upon the application of rigorous experimental design and data analysis. The endpoints used can be in situ or excision. Each of these has advantages and disadvantages to the ‘‘drug hunter’’ searching for improved treatments. Keywords Tumor growth delay • Xenografts • Isobolograms • Drug distribution • Enzastaurin • Intratumoral vessels
23.1 Introduction The field of cancer research only recently came to the forefront of human scientific endeavor and took advantage of experience gained in studying other disease processes. Over many years prior to the formal investigation of malignant disease, researchers had worked out scientific methodology and recognized the importance of laboratory models for infectious diseases, allowing rapid progress in antibacterial
B.A. Teicher (*) Genzyme Corporation, 49 New York Avenue, Framington, MA 01701-9322, USA e-mail: [email protected] B.A. Teicher (ed.), Tumor Models in Cancer Research, Cancer Drug Discovery and Development, DOI 10.1007/978-1-60761-968-0_23, © Springer Science+Business Media, LLC 2011
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drug development. Cancer research also benefited from the early research of the 1950s and 1960s, which took a very orderly and rigorously scientific approach to the development of in vivo models and to the development of the most informative endpoints available from experiments suing in vivo tumor models.
23.2 Ascites Tumors The science of preclinical modeling of anticancer therapies began in the 1950s, but the establishment of guidelines for experimental quality and end point rigor can be attributed in large part to the group headed by Howard Skipper at the KetteringMeyer Laboratory affiliated with Sloan-Kettering Institute, Southern Research Institute in Birmingham, Alabama. In the mid-1960s, this group published a series of reports on the criteria of “curability” and on the kinetic behavior of leukemia cells in animals and the effects of anticancer chemotherapy. The principles put forth in these reports were derived directly from the behavior of bacterial-cell populations exposed to antibacterial agents, and were based upon experimental findings in mice bearing intraperitoneally impla
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