Conflict of interests: none to declare.
Why imatinib remains an exception of cancer research†
Article first published online: 20 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 4, pages 665–670, April 2013
How to Cite
Horne, S. D., Stevens, J. B., Abdallah, B. Y., Liu, G., Bremer, S. W., Ye, C. J. and Heng, H. H.Q. (2013), Why imatinib remains an exception of cancer research. J. Cell. Physiol., 228: 665–670. doi: 10.1002/jcp.24233
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 27 SEP 2012 07:37AM EST
- Manuscript Accepted: 27 SEP 2012
- Manuscript Received: 19 SEP 2012
- U.S. Department of Defense. Grant Number: GW093028
- SeeDNA, Inc.
- The National Chronic Fatigue and Immune Dysfunction Syndrome Foundation and the Nancy Taylor Foundation for Chronic Diseases
- Susan G. Komen Breast Cancer Foundation
The archetype driving the drug targeting approach to cancer therapy is the success of imatinib against chronic phase chronic myeloid leukemia (CML-CP). Molecular targeting success of this magnitude has yet to be repeated for most solid tumors. To answer why imatinib remains an exception of cancer research, we summarize key features and patterns of evolution that contrast CML-CP from prostate cancer, an example of a solid tumor that also shares a signature fusion gene. Distinctive properties of CML-CP include: a large cell population size that is not geographically constrained, a highly penetrant dominant oncogene that sweeps the entire cell population, subsequent progressive and ordered clonal genetic changes, and the effectiveness of molecular targeting within the chronic phase, which is comparable to the benign phase of solid tumors. CML-CP progression resembles a clonal, stepwise model of evolution, whereas the pattern of solid tumor evolution is highly dynamic and stochastic. The distinguishing features and evolutionary pattern of CML-CP support why the success of imatinib does not carry over to most solid tumors. Changing the focus of cancer research from a gene-based view to a genome-based theory will provide insight into solid tumor evolutionary dynamics. J. Cell. Physiol. 228: 665–670, 2013. © 2012 Wiley Periodicals, Inc.