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Review Article
Heterotransplant mouse model cohorts of human malignancies: a
novel platform for systematic preclinical efficacy evaluation of drugs
(SPEED)
Ashutosh K. Pathak, Manisha Bhutani, Pierre Saintigny, Li Mao
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center,
Houston, TX 77030; Internal Medicine, Michigan State University, East Lansing, MI 48824; and Discovery Medicine
& Clinical Pharmacology (DMCP) Oncology/Immunology, Bristol-Myers Squibb Company, Princeton, NJ 08543,
USA
Received November 1, accepted November 3 and available online November 15, 2008
Abstract: Advances in molecular biology demonstrate that cancer is heterogeneous disease necessitating a
personalized management approach. This is introducing a paradigm shift in clinical trial designs where
molecular characterization of cancers is assuming importance equal to (or even more than) the traditional
histologic diagnosis as the eligibility criterion for randomized clinical trials of new therapies. Recommendations
have been made to gather the molecular information from clinical phase II trials distinguishing responding from
non responding tumors for subsequent planning of large scale phase III trials. However by the time we reach
phase II level, more than a billion dollars apart from years of research have been invested. It would be therefore
prudent to conceptualize laboratory based platforms to obtain the proof of concept as early as possible, even
before embarking upon the pivotal clinical trials. In this regard, we hereby propose and detail a novel preclinical
platform incorporating the existing mouse models to address the issue of tumor heterogeneity in a systematic
manner through creation of a setting similar to phase II trials in human patients. By providing critical information
about a drug’s efficacy and the molecular determinants of response early on, this platform would potentially
provide a solid foundation to build avant-garde clinical trials integrating recent advances in molecular medicine.
(AJTR811001).
Key Words: Cancer, heterotransplant, animal model, therapeutics, drug development
Full Text PDF
Address all correspondence to:
Li Mao, MD
Molecular Biology Laboratory
Department of Thoracic/Head and Neck Medical Oncology, Unit 432
The University of Texas M.D. Anderson Cancer Center
P.O. Box 301402
Houston, TX 77030
E-mail: lmao@mdanderson.org
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