Reviewing the last 10 years of cancer research much as
they might the production of a play complete with cast
members, opening acts and an ever-twisting plot, two of the
most cited names in science say that one of the most
promising roles that newly discovered cancer genes may
perform is in early detection, which likely will be as
important as new treatments.
In an editorial review that is the centerpiece of
Nature Medicine's 10th anniversary August issue,
Johns
Hopkins Kimmel Cancer Center scientists Bert Vogelstein
and Kenneth Kinzler used a lengthy Broadway metaphor to
suggest that the conquest of cancer is a drama that has
lots more acts to come, some of them destined to refocus
large parts of the national research effort.
"The best chance of managing these diseases in the
next few decades relies on taking advantage of the genes we
now know lie at the heart of the process," says Vogelstein,
who is the world's most influential scientist, according to
citation rankings by the Institute of Scientific
Information. "Cancer already is curable when it's caught
early. New methods of detecting cancers, although less
dramatic and not as popular, offer very promising
approaches for limiting cancer deaths in the future."
In the past, the Johns Hopkins scientists argue, the
lack of better "scripts" including key gene characters
hindered drug development and early diagnostic efforts.
With a refined cast of characters, more researchers may
steer their efforts to better diagnostic and therapeutic
strategies, which may have a greater impact on cancer death
rates.
In their review, Vogelstein and Kinzler describe the
progress in understanding cancer and the roles of nearly
100 genes that have been definitively linked to the
disease. The opening act introduces three kinds of genes
that regulate cancer growth pathways. Oncogenes, when
altered, get stuck in active duty, much as a stuck
accelerator in a car. In opposite roles, tumor suppressor
genes act as malfunctioning brakes. Finally, faulty
stability genes act like bad auto mechanics, failing to
repair mistakes made in the DNA code during replication or
exposure to mutating agents. Genes that control blood
supply to a tumor are cast in important supporting
roles.
The central plot involves the cell growth pathways
that these genes control — discoveries that
demonstrate how each gene affects a cascade of protein
production that is necessary for cancer development.
Remarkably, the majority of these genes, which vary
considerably in different cancers, converge on a relatively
small number of similar pathways that direct cancer growth,
providing a common story line.
"Researchers know many of the genes involved in cancer
development and are learning how to put the entire cast
together, and we are beginning to understand the best ways
to apply gene discoveries to help patients," Kinzler says.
"The last decade of gene discovery now sets the stage for
this sequel, which will include new methods for early
detection as well as targeted therapeutics."
In addition to developing more sophisticated tools for
early detection of tumors, Vogelstein and Kinzler say that
other areas of future research should include better models
for testing targeted therapies and investigating the
functions of novel genes auditioning for leading roles in
the cancer process.
Vogelstein and Kinzler have been studying the genetics
of cancer for more than 20 years and have made pivotal
discoveries of genes and pathways that lead to cancer,
including those involving p53, APC, mismatch repair and
Gli. Vogelstein is the Clayton Professor of Oncology at
Johns Hopkins and an investigator with the Howard Hughes
Medical Institute. Kinzler is professor of oncology and
with Vogelstein co-directs the Molecular Genetics
Laboratory at the Kimmel Cancer Center.
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