Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CANCER AS A MICROEVOLUTIONARY PROCESS
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an undetected micrometastasis will remain dormant for many years, only to
reveal its presence by erupting into growth to form a large secondary tumor long
after the primary tumor has been removed.
Many Properties Typically Contribute to Cancerous Growth
Clearly, to produce a cancer, a cell must acquire a range of aberrant properties—a
collection of subversive new skills—as it evolves. Different cancers require different
combinations of these properties. Nevertheless, cancers all share some common
features. By definition, they all ignore or misinterpret normal social controls
so as to proliferate and spread where normal cells would not. These defining properties
are commonly combined with other features that help the miscreants to
arise and thrive. A list of the key attributes of cancer cells in general would include
the following, all of which we have just discussed:
1. They grow (biosynthesize) when they should not, aided by a metabolism
shifted from oxidative phosphorylation toward aerobic glycolysis.
2. They go through the cell-division cycle when they should not.
3. They escape from their home tissues (that is, they are invasive) and survive
and proliferate in foreign sites (that is, they metastasize).
4. They have abnormal stress responses, enabling them to survive and continue
dividing in conditions of stress that would arrest or kill normal cells,
and they are less prone than normal cells to commit suicide by apoptosis.
5. They are genetically and epigenetically unstable.
6. They escape replicative cell senescence, either by producing telomerase or
by acquiring another way of stabilizing their telomeres.
In the next section of the chapter, we examine the mutations and molecular
mechanisms that underlie these and other properties of cancer cells.
Summary
Cancer cells, by definition, grow and proliferate in defiance of normal controls (that
is, they are neoplastic) and are able to invade surrounding tissues and colonize distant
organs (that is, they are malignant). By giving rise to secondary tumors, or
metastases, they become difficult to eradicate by surgery or local irradiation. Cancers
are thought to originate from a single cell that has experienced an initial mutation,
but the progeny of this cell must undergo many further changes, requiring
additional mutations and epigenetic events, to become cancerous. Tumor progression
usually takes many years and reflects the operation of a Darwinian-like process
of evolution, in which somatic cells undergo mutation and epigenetic changes
accompanied by natural selection.
Cancer cells acquire a variety of special properties as they evolve, multiply, and
spread. Their mutant genomes enable them to grow and divide in defiance of the
signals that normally keep cell proliferation under tight control. As part of the evolutionary
process of tumor progression, cancer cells acquire a collection of additional
abnormalities, including defects in the controls that permanently stop cell
division or induce apoptosis in response to cell stress or DNA damage, and in the
mechanisms that normally keep cells from straying from their proper place. All of
these changes increase the ability of cancer cells to survive, grow, and divide in their
original tissue and then to metastasize, founding new colonies in foreign environments.
The evolution of a tumor also depends on other cells present in the tumor
microenvironment, collectively called stromal cells, that the cancer attracts and
manipulates.
Since many changes are needed to confer this collection of asocial behaviors, it is
not surprising that most cancer cells are genetically and/or epigenetically unstable.
This instability is thought to be selected for in the clones of aberrant cells that are
able to produce tumors, because it greatly accelerates the accumulation of the further
genetic and epigenetic changes that are required for tumor progression.