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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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