Page 104 - 20dynamics of cancer

PROGRESSION DYNAMICS 89

comparative models are often rejected a priori because they do not con-
tain all known processes. The reasoning seems to be: how can a model
be useful if a known process is left out? All known processes are added
in; fits are obtained; little is learned; quantitative analysis is abandoned.
A model is not a synthesis of all known observations; a model is a tool
to test one’s ability to predict the behavior of a system. If one cannot say
how the system changes when perturbed, then one does not understand
the system. To study perturbations most effectively, formulate and test
the simplest comparative theories.

5.2 Observations to Be Explained

In this section, I briefly list a few puzzles—just enough to set the
context. Chapter 2 provided a more complete review of the observations
on age-specific incidence.
The difference in incidence curves between inherited and sporadic
cancers provides the most striking observation (Knudson 1971, 2001).
In the simplest case, the inherited form of a cancer arises in those who
carry a defect in a single allele. For example, a carrier with a mutant
APC allele typically develops numerous independent colon tumors in
midlife. By contrast, sporadic (noninherited) cases mostly occur later in
life.
The comparison between inherited and sporadic incidence curves pre-
sents an opportunity to test how particular mutations affect the rate of
cancer progression. Figure 2.6 compares incidence data between spo-
radic cancers and inherited cancers in carriers of a mutation to a sin-
gle allele. Comparison of incidence curves between experimentally con-
trolled genotypes of rodents provides an exceptional opportunity to test
hypotheses. Figure 2.7 illustrates the sort of data that can be obtained.
Later, I will provide methods to analyze those data with regard to quan-
titative models of progression dynamics.
Six additional patterns in the incidence data suggest the kinds of puz-
zles that dynamical theories of progression must explain.
First, incidence accelerates slowly with age for some cancers, such
as melanoma, thyroid, and cervical cancers. By contrast, other cancers
accelerate more rapidly with age, such as colorectal, bladder, and pan-
creatic cancers (Figure 2.3).