Abstract
Oncology, as a therapeutic area, is characterized by a desperate medical need for new drugs; the use of drugs that kill cells and which are consequently often toxic; and rates of failure in expensive Phase III trials that eclipse many other disease areas. The poor performance of most investigational cancer drugs implies that the standard preclinical disease models are faulty or, at least, improperly used. Some studies, however, support the view that cancer models can be highly effective, but only when selected and interpreted with care.
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References
Kola, I. & Landis, J. Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Discov. 3, 711–715 (2004).
Gorre, M. E. & Sawyers, C. L. Molecular mechanisms of resistance to STI571 in chronic myeloid leukemia. Curr. Opin. Hematol. 9, 303–307 (2002).
Kamb, A. Consequences of nonadaptive alterations in cancer. Mol. Biol. Cell. 14, 2201–2205 (2003).
Roberts Jr., T. G. et al. Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. JAMA 292, 2130–2140 (2004).
Ishii, N., Robert, M., Nakayama, Y., Kanai, A. & Tomita, M. Toward large-scale modeling of the microbial cell for computer simulation. J. Biotechnol. 113, 281–294 (2004).
Oskoglou-Nomikos, T., Pater, J. L. & Seymour, L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin. Cancer Res. 9, 4227–4239 (2003).
Yingling, J. M., Blanchard, K. L. & Sawyer, J. S. Development of TGF-β signaling inhibitors for cancer therapy. Nature Rev. Drug Discov. 3, 1011–1022.
Peterson, J. K. & Houghton, P. J. Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development. Eur. J. Cancer 40, 837–844 (2004).
Druker, B. J. Imatinib as a paradigm of targeted therapies. Adv. Cancer Res. 91, 1–30 (2004).
Dancey, J. E. Predictive factors for epidermal growth factor receptor inhibitors — the bull's-eye hits the arrow. Cancer Cell 5, 411–415 (2004).
Tuveson, D. A. et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 20, 5054–5058 (2001).
Griffin, J. D. FLT3 tyrosine kinase as a target in acute leukemias. Hematol. J. 5, S188–190 (2004).
Slamon, D. & Pegram, M. Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials. Semin. Oncol. 28, 13–19 (2001).
Weisberg, E. & Griffin, J. D. Resistance to imatinib (Glivec): update on clinical mechanisms. Drug Resist. Updat. 6, 231–238 (2003).
Scherf, U. et al. A gene expression database for the molecular pharmacology of cancer. Nature Genet. 24, 236–244 (2000).
Jonkers, J. & Berns, A. Conditional mouse models of sporadic cancer. Nature Rev. Cancer 2, 251–265.
Johnson, J. I. et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br. J. Cancer 84, 1424–1431 (2001)
Wong, S. L. et al. Proc. Natl Acad. Sci. USA 101, 15682–15687 (2004).
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Kamb, A. What's wrong with our cancer models?. Nat Rev Drug Discov 4, 161–165 (2005). https://doi.org/10.1038/nrd1635
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DOI: https://doi.org/10.1038/nrd1635
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