Re: Challenging Conventional Wisdom on Cancer

From: Tim <>
Date: Fri Aug 19 2005 - 21:54:14 EDT

Genomic rearrangements, of which aneuploidy represents one subclass,
have the attention of cancer researchers*. Well, one group of many
mechanism being studied. It is known that the development of many
cancers may involve stepwise progression from precancerous to malignant
stages**. There is also discussion of cancer 'stem cells'.
Unfortunately, it is difficult at this time to prevent progression in
most cases: We can find that abnormal cells exist (sometimes, although
even this is not always easy) in somebody, but that is a separate issue
from being able to do something about it. There is some work that is
examining how to block progression to more malignant states but in this
regard the safety of treatments becomes a terribly important factor.
Cancer drugs are not easy on the body. Agents that disrupt critical cell
functions necessary for cancer cell growth can hit other pathways in
non-cancerous cells and produce serious side effects. These effects are
acceptable for patients with active cancers, but the risk/benefit ratio
is much worse for treating the much larger population of *potential*
cancer progressors. Preventive treatments must be well tolerated,
efficacious and cost effective. Safety is a big concern because
treatments would be long-term and given to a group of people where most
might not otherwise develop the particular cancer. Efficacy is
particularly difficult to assess and would require long (read: expensive
and large) clinical trails. It's not clear how the FDA approval process
will work.

Meanwhile, developing treatments for "active" cancers will continue to
be a major focus (prevention is never 100%). I have read some criticisms
of "one-gene" approaches to treatment, but I think those tend to be
overstated for the sake of trying to create a contrast with an
"alternate" theory. For cancer cells to replicate, they have to evade
many of the normal and common signal pathways that would otherwise cause
improperly dividing cells to halt and/or suicide (apoptosis). It does
not matter if cancer cells have 1, 2, 3, or 4 times the normal
complement of genes; they *all* still have to get around growth
checkpoints. Cancers can often be grouped by which pathways they use to
circumvent replication blocks. Thus it is possible to attack cancer
cells by targeting specific pathways or classes of regulators. The
success rate of treatments is varied but some, like Lance Armstrong are
finding benefit. It is likely that multidrug treatment regimes tailored
to specific pathways will be required to increase efficacy. But these
are hard evaluations to perform. In many instances, there are not enough
patients to run trials of various combinations.

Interestingly, if we do consider what early-stage treatments would be
required to prevent progression to cancer, a very similar approach will
probably be used. Once again, mechanisms that allow aberrant chromosomal
segregation and instability tend to follow common paths. The same is
true for mechanisms that could induce apoptosis in cells with these
defects. These pathways will be targeted in similar way. And we'd better
hope this is the case because having a limited set of causes at least
provides a reasonable chance for some success.

* Abnormal chromosome segregation is another mechanism for creating
genetic variation which can be exploited in evolutionary processes. It
also plays a role in some forms of speciation.

** Interesting paper here. Note Dr. Frank's department:

Tim I
Received on Fri Aug 19 21:56:14 2005

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