Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy

M Chesi; GM Matthews; VM Garbitt; SE Palmer; J Shortt; M Lefebure; AK Stewart; RW Johnstone; P Leif Bergsagel

Journal article

Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy

M Chesi, GM Matthews, VM Garbitt, SE Palmer, J Shortt, M Lefebure, AK Stewart, RW Johnstone, P Leif Bergsagel

Blood | AMER SOC HEMATOLOGY | Published : 2012

DOI: 10.1182/blood-2012-02-412783

Abstract

The attrition rate for anticancer drugs entering clinical trials is unacceptably high. For multiple myeloma (MM), we postulate that this is because of preclinical models that overemphasize the antiproliferative activity of drugs, and clinical trials performed in refractory end-stage patients. We validate the Vk*MYC transgenic mouse as a faithful model to predict single-agent drug activity in MM with a positive predictive value of 67% (4 of 6) for clinical activity, and a negative predictive value of 86% (6 of 7) for clinical inactivity. We identify 4 novel agents that should be prioritized for evaluation in clinical trials. Transplantation of Vk*MYC tumor cells into congenic mice selected fo..

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University of Melbourne Researchers

Ricky Johnstone Author

Grants

Awarded by National Institute on Aging

Funding Acknowledgements

This work was supported by National Institutes of Health grant AG20686, National Cancer Institute grant CA136671 (P.L.B.), and by the Multiple Myeloma Research Foundation (M.C.). R.W.J. is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and is supported by NHMRC Program and Project grants, the Susan G. Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, The Victorian Cancer Agency, The Leukemia Foundation of Australia, Victorian Breast Cancer Research Consortium, and the Australian Rotary Health Foundation. G.M.M. is supported by an Australian Biomedical Fellowship (Peter Doherty) from the NHMRC. J.S. is supported by the Leukemia Foundation of Australia and the Cooperative Research Center for Biomedical Imaging Development. M.L. is supported by the Leukemia Foundation of Australia. The laboratory of R.W.J. receives research funding from Novartis for studies involving panobinostat.