Page 51 - 20dynamics of cancer

3 Multistage Progression

Several checks prevent uncontrolled proliferation of cells. Normal cells
commit suicide when they cannot pass various quality control tests; a
built-in counting mechanism limits the number of times a cell can divide;
structural rigidity and physical partitions in tissues prevent expansion
of abnormal cellular clones. In this chapter, I describe how cancer devel-
ops by sequential changes to cells and tissues that bypass these normal
checks on tissue growth.
The first section defines the word progression to include all of the
changes that transform cells from normal to cancerous. Earlier litera-
ture split the stages of transformation into initiation, promotion, and
progression to metastasis. Some tumors may develop through these
particular stages, but those stages can be difficult to discern and are
not universal. So I use progression in the general sense of development
from the first to the final stages.
The second section considers the meaning of the commonly used
phrase multistage progression. I focus on how the rates of change in
progression affect the age-onset patterns of cancer. In this framework,
the multiple stages of progression describe the rate-limiting steps. I
use this framework in later chapters to formulate and test quantitative
hypotheses about how particular events affect cancer.
The third section summarizes multistage progression in colorectal
cancer. That cancer provides the clearest example of distinct morpho-
logical and genetic stages in tumor development.
The fourth section describes alternative pathways of multistage pro-
gression in colorectal cancer. The distinct morphological and genetic
pathways are probably governed by different rate processes. In general,
cancer of a particular tissue may be heterogeneous with regard to the
pathways and rate processes of progression.
The fifth section provides a transition into the second half of the chap-
ter, in which I summarize the kinds of changes that accumulate during
progression.