Biomedical Engineering Reference
In-Depth Information
6.1
MODELING CANCER AS A COMPLEX
ADAPTIVE SYSTEM: GENETIC
INSTABILITY AND EVOLUTION
Kenneth J. Pienta
University of Michigan Comprehensive Cancer Center, Ann Arbor
Cancer is the second leading cause of death in the United States, claiming over 500,000
lives annually. While we now understand that cancer is a disease of genetic mutation, it is
still difficult to describe how cancer arises from normal cells. Describing carcinogenesis
in terms of a complex adaptive system reacting to the forces of Darwinian evolution gives
a framework to understand tumorigenesis. This understanding is leading to new para-
digms of cancer therapy, including multidisciplinary approaches to attack the cancer as a
heterogeneous group of diseases as well as the development of aptamer molecular evolu-
tion techniques to design therapeutics to evolve as the cancer mutates.
1.
INTRODUCTION
Generally, we consider evolution the fundamental strategy of life at the
level of the organism. It is how we became who we are via interplay of genetic
variation and phenotypic selection (1). The premise of evolution is that genes,
and hence gene variants, are selected because they encode functions that in some
way improve the chance of organism survival (2,3). This premise can be passed
onto the level of the cancer cell. A tumor can be considered to be an organism or
species that is able to speed up the evolutionary process by millions of years to
select properties that help it survive and thrive within the macrocosm of the hu-
man body (4-6).
Address correspondence to: Kenneth J. Pienta, University of Michigan Comprehensive Cancer Cen-
ter, 1500 East Medical Center Drive, 7303 CCGC, Ann Arbor, MI 48109-0946 (kpienta@umich.
edu).
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