Journal article

In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas

Kylie D Mason, Cassandra J Vandenberg, Clare L Scott, Andrew H Wei, Suzanne Cory, David CS Huang, Andrew W Roberts

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2008

Abstract

Deregulated Myc expression drives many human cancers, including Burkitt's lymphoma and a highly aggressive subset of diffuse large cell lymphomas. Myc-driven tumors often display resistance to chemotherapeutics because of acquisition of mutations that impair the apoptosis pathway regulated by the Bcl-2 protein family. Given the need to identify new therapies for such lymphomas, we have evaluated the efficacy of ABT-737, a small molecule that mimics the action of the BH3-only proteins, natural antagonists of the prosurvival Bcl-2 proteins. ABT-737 selectively targets certain prosurvival proteins (Bcl-2, Bcl-x(L), and Bcl-w) but not others (Mcl-1 and A1). We treated mice transplanted with lymp..

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Grants

Awarded by Australian National Health and Medical Research Council


Awarded by U.S. National Cancer Institute


Awarded by Leukemia and Lymphoma Society Specialized Center for Research


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

Wethank Abbott Laboratories for providing ABT-737; our colleagues for useful discussions; F. Battye, D. Cooper, H. lerino, E. Jansen, A. Naughton, K. Pioch, G. Siciliano, A. Srikumar, A. Wiegmans for excellent technical assistance; and L. O'Reilly for reagents. This work was supported by the Australian National Health and Medical Research Council Program Grants 461221 and 461219 and Fellowships (to C.J.V., C.L.S., D.C.S.H., and A.W.R.), U.S. National Cancer Institute Grant CA43540, Leukemia and Lymphoma Society Specialized Center for Research Grant 7015-02 and a fellowship (to C.L.S.), Australian Cancer Research Foundation (Centre for Therapeutic Target Drug Discovery), Cancer Council of Victoria (K.D.M.), Leukemia Foundation (A.H.W.) and the Victorian Cancer Agency (K.D.M.).