Biomedical Engineering Reference
In-Depth Information
cell down the cancer pathway. Similarly, an antelope could inherit a rare allele
and be born an albino, immediately putting it at a disadvantage to the other,
camouflaged, members of the herd. Cancer cells are subject to a wide variety of
genotoxic perturbations that could potentially cause mutation and selective pres-
sure. These are mirrored by the same types of insults that a herd of animals must
survive—for example, changes in weather, ability to withstand infections. These
risks are modulated by inherent factors: in cells, for example, drug metabolizing
enzymes; in animals, muscle fiber length (running speed). The risks are also
modulated by extrinsic agents. Are there chemoprevention agents present for
cells? For animals such agents include the presence of other protective species,
the ability to migrate, and the number of adult males present to ward off attack.
3.
CANCER EVOLUTION IN THE CONTEXT OF RECENT
HUMAN EVOLUTION
Each cancer and the cancer cells that comprise it have a distinct phenotype;
however, cancers do share a group of common characteristics (4,11,12). A tu-
mor is the result of a collection of cancer cells that are actively acquiring muta-
tions which allow the emergence of a successful clone of cells. This is a highly
inefficient process, and tumors are filled with clones of cells that will not sur-
vive long term and are undergoing apoptosis (programmed cell death) as a result
of harmful mutations and hypoxia, as well as other insults including immune
surveillance. Some cells manage to acquire enough mutations and acquire the
characteristics of a successful cancer cell. This can be compared, at least on one
level, to the evolution of human civilization. A key difference between these two
types of evolution is that we believe human beings evolved societies as a result
of conscious decisions that increased our chances for species survival. To under-
stand cancer clonal expansion, we have to explain cancer cell growth and sur-
vival in terms of an unconscious process. This is much more likely to be
modeled by early evolution, when we pulled ourselves out of the sea and be-
came multicellular organisms. However, the exercise of comparing a successful
cancer cell successfully colonizing a new metastatic site to human civilization
and colonization is worthwhile (see Table 2).
3.1. Unlimited Replicative Potential
Cancer cells are immortal. This does not mean that each cell itself lives for-
ever (just like humans), but that the cell population doubles without limit and
creates uncontrolled clonal expansion. In non-cancerous cells, a cell can double
approximately 50 times before it undergoes senescence and dies (13). This has
been termed the Hayflick number and is the result of an internal cell doubling
