The evolutionary mechanism of cancer
Article first published online: 8 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 109, Issue 6, pages 1072–1084, 15 April 2010
How to Cite
Heng, H. H.Q., Stevens, J. B., Bremer, S. W., Ye, K. J., Liu, G. and Ye, C. J. (2010), The evolutionary mechanism of cancer. J. Cell. Biochem., 109: 1072–1084. doi: 10.1002/jcb.22497
- Issue published online: 26 MAR 2010
- Article first published online: 8 MAR 2010
- Manuscript Accepted: 14 DEC 2009
- Manuscript Received: 7 DEC 2009
- Susan G. Komen Breast Cancer Foundation
- SeeDNA Biotech, Inc.
- genome theory;
- cancer evolutionary mechanism;
- genomic instability;
- non-clonal chromosome aberrations (NCCAs)
Identification of the general molecular mechanism of cancer is the Holy Grail of cancer research. Since cancer is believed to be caused by a sequential accumulation of cancer gene mutations, the identification, characterization, and targeting of common genetic alterations and their defined pathways have dominated the field for decades. Despite the impressive data accumulated from studies of gene mutations, epigenetic dysregulation, and pathway alterations, an overwhelming amount of diverse molecular information has offered limited understanding of the general mechanisms of cancer. To solve this paradox, the newly established genome theory is introduced here describing how somatic cells evolve within individual patients. The evolutionary mechanism of cancer is characterized using only three key components of somatic cell evolution that include increased system dynamics induced by stress, elevated genetic and epigenetic heterogeneity, and genome alteration mediated natural selection. Cancer progression represents a macro-evolutionary process where karyotype change or genome replacement plays the key dominant role. Furthermore, the recently identified relationship between the evolutionary mechanism and a large number of diverse individual molecular mechanisms is discussed. The total sum of all the individual molecular mechanisms is equal to the evolutionary mechanism of cancer. Individual molecular mechanisms including all the molecular mechanisms described to date are stochastically selected and unpredictable and are therefore clinically impractical. Recognizing the fundamental importance of the underlying basis of the evolutionary mechanism of cancer mandates the development of new strategies in cancer research. J. Cell. Biochem. 109: 1072–1084, 2010. © 2010 Wiley-Liss, Inc.