University Of Chicago Medical Center
Completion
of the human genome project will influence the general framework
for anticancer drug development but not fundamentally alter it
any time soon predict two cancer specialists in a commentary in
the March issue of Nature Medicine.
In "Gazing
into a crystal ball -- Cancer therapy in the post-genomic era,"
Mark Ratain, M.D., of the University of Chicago, and Mary Relling,
Pharm.D., of St Jude's Children's Research Center, the chair and
vice-chair of the Pharmacogenetics of Anticancer Agents Research
Group, caution that before genetic information allows doctors
to tailor therapy to each patient, much more work must be completed.
"Although
access to a patient's genetic information will someday make cancer
therapy more effective," note the authors, many "technical,
experimental and clinical advances must be made before this day
can arrive."
"The
basic process," they add, "of target identification,
drug discovery, preclinical and clinical work will be facilitated
-- but not necessarily revolutionized -- by the human genome sequence."
For guidance
in predicting the future, Ratain and Relling turn to five basic
principles of prognostication, as formulated by technology columnist
Robert X. Cringely, host of the PBS-TV miniseries "Triumph
of the Nerds." The five principles are:
-- 1) We tend
to overestimate the amount of change that will take place in the
short term.
-- 2) We tend
to underestimate the amount of change that will take place in
the long term.
-- 3) The
more specific a prediction, the less likely it is to be correct.
-- 4) Past
performance is a predictor of future results, but not a good one.
-- 5) The
most reliable predictions are those that follow established trends.
The cost of
individualized therapy appears to confirm principle one. While
the genome project has reported the sequence of a few volunteers,
individualized therapy will require personal sequence information
from each patient. At the current rate, that would cost about
$120 million per person. If sequencing costs continue to fall
by about 50 percent a year, in line with rule five, the cost would
become reasonable, at around $500, in 18 years.
Their sobering
point is that despite this remarkable achievement, and even if
we are able to follow it by mapping out all the genetic changes
that play a role in cancer, a daunting amount of basic biology
and pharmacology will remain to be tackled.
Consequently,
cancer research is about to enter a transitional period, in which
there will be "an abundance of genomic data," note the
authors, "but an inability to use it to fully predict cancer
treatment outcomes."
One sterling
example is the recent success of STI-571, an unusually potent
medication that targets a crucial gene defect in one particular
type of leukemia. That gene defect, a translocation of chromosome
9 and 22, was first described by Janet Rowley of the University
of Chicago -- in 1973, 28 years ago.
"Many
of the root causes of cancer lie in genetic abnormalities,"
note the authors. Publication of the human genome project is a
necessary first step in optimizing treatment of cancer and other
human diseases. It will help identify the molecular differences
between normal tissue and tumors, speed the identification of
new treatment targets, improve classification of tumors and facilitate
individual drug dosing -- which is the goal of the Pharmacogenetics
Group.
Rule two --
we tend to underestimate long-term change -- applies to those
who say this day will never come. But the more pessimistic rules
one, four and five should remind us that the genome project was
only the first step of a very long journey.
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