effectively target the altered signaling networks identified by
genomic analyses. Further, the goal is to make this strategy part of
standard of care for the treatment and prevention of cancer.
Colorectal cancer is one of the cancers for which wholesale
genomic analyses have been completed (115). Researchers
examined all of the genes in pairs of normal and cancerous tissue
of more than 200 patients with colorectal cancer. They found that
most of the genetic alterations detected in a significant portion of
the cancers affected just five signaling networks. Of note, one
signaling network, called the WNT signaling pathway, was altered
in nearly all of the cancers (93%), suggesting that drugs that block
this pathway might benefit many patients with colorectal cancer. In
addition, 5% of the cancers had extra copies of the HER2 gene,
indicating that trastuzumab and pertuzumab might be effective
therapies for individuals with these cancers since they successfully
treat breast and stomach cancers that harbor additional HER2
genes. The data from this study highlight the potential that large-scale genomic technologies have for identifying new drug targets
for individual cancer types, but much more work is needed if we
are to deliver on this promise.
Currently, the greatest use of large-scale genomic analyses
remains in the research setting, as highlighted by the work of
Joyce O’Shaughnessy, M.D., where it can guide the development
of new cancer drugs, direct the repurposing of established
Figure 20: Genomic Medicine: Finding
the Trees in the Forrest. Whole genome
sequencing of three different patients
(blue, red and purple) reveals many
individual genetic alterations in each
patient. It would be impossible to
administer targeted therapies to treat each
of the defects; however, when the patients’
genomes are compared, three potential
therapeutic targets—and thus treatment
therapies to treat novel genetic aberrations and inform clinical
research by assigning the most appropriate patients to the best
clinical trials. To date, wholesale genomic analysis has been
successfully used to guide the choice of therapy for a few patients
in the research setting, suggesting the day when it becomes part of
standard practice is close at hand. Clearly, these advances are an
early step toward a future where most cancer treatment and
prevention strategies are based on both a person’s genetic makeup
and the genetic makeup of their specific cancer.
If this is to become a reality, the cost of deciphering a person’s
genetic code and that of their particular cancer must drop even
further than it has in the past decade The cost is estimated to have
Baylor Charles A. Sammons
Cancer Center at Dallas
• Employs 250 people.
• Treats more than 8,000 unique
patients each year.
• Accommodates more than 80,000
outpatient visits each year.
• Has a clinical research program that
offers more than 100 clinical trials at
any one time, with close to 800
patients participating annually.