Models for cancer

Cancer Drug Discovery and Development: Tumor Models in Cancer Researchedited by B.A. Teicher, Humana Press, 2002. $175 (hardback) (690 pages) ISBN: 0-89603-887-4What a wonderful time for experimental oncology! A confluence of theoretical and technical advances is contributing to our greater understanding of the biological basis of neoplastic growth and encouraging optimism that these advances will hasten prevention and cure. We now recognize that neoplastic cells not only escape growth restrictions normally enforced by cell–cell and cell–matrix interactions, but also actively subvert these paracrine interactions by causing stromal cells to stimulate epithelial proliferation. Molecular classification of cancer subtypes by microarray analysis permits individualization of therapy, and proteomics will soon present a global view of protein–protein interactions. We have the ability to ‘design’ mice wherein genes of interest, such as proto-oncogenes, tumor suppressors and genes regulating inflammation, angiogenesis, and apoptosis can be overexpressed or inactivated in an inducible and/or cell-specific manner to assess their contributions to oncogenesis. The purpose of this book is to allow clinical oncologists, as well as those who already study cancer in rodents, to gain a more sophisticated appreciation of these models.This comprehensive compilation of animal models describes xenografts (human cells implanted into immunocompromised mice), syngeneic rodent tumors (neoplastic mouse cells implanted into a compatible host), chemical carcinogen-induced primary tumors that progress from normal cells to benign tumors to malignancy, tumors in genetically engineered mice, and models of metastasis. Additional sections describe tumors at specific organ sites and principles related to cancer research such as stem cells, bone marrow transplantation and general anesthesia.The general standard of writing in this multi-authored, 34-chaptered text is high, and several chapters are noteworthy. The introductory chapter by J.R. Steadman offers an historical perspective on the utility of xenografts for drug discovery. He divides this research into three eras. The first consisted of identifying drugs that kill leukemic cell xenografts, which helped cure childhood leukemia and illustrated general strategies for conducting chemotherapeutic drug discovery. During the second, similar attempts to find effective agents against solid tumors have unfortunately failed. The current approach is to understand the mechanisms key to neoplastic conversion and growth in order to introduce novel molecular targets for chemotherapy. D.J. Dykes and W.R. Waud examined the relative merits of human xenografts and syngeneic rodent transplants. R.M. Hoffman's use of cells transfected with green fluorescent protein to follow the course of micrometastases provides information about a fascinating experimental tool. J. Schwartz and X. Gu demonstrate a bimodal effect of β-carotene on a hamster oral tumor in which low doses inhibit carcinogenesis, while higher drug doses enhance it. Awareness of this work could perhaps have averted the catastrophic human trial in which high β-carotene doses increased lung cancer incidence in smokers. Most animal models of cancer primarily concern early benign lesions, whereas malignant conversion and tumor dissemination have not been studied as widely: the chapter on metastasis by S.A. Eccles addresses this deficiency.However, this compilation is not ‘complete’. Material relating to angiogenesis and descriptions of conditional gene modifications are absent. Although our genomes are over 98% identical, major differences between humans and mice in when and where common genes are expressed urges caution in translating what is learned from animal studies. Nonetheless, wise applications, as this book points out, will yield helpful information, such as common signalling pathways, obtainable from no other source. Consequently, I will recommend that our library purchases it and that graduate students in my tumor biology class read selected chapters.