Each person’s body handles drugs differently. These
differences are a result of subtle variations in the genome of
each individual. The use of advanced genome sequencing
technologies to study the influence of genetic variation on
patients’ responses to drugs is an area of research called
pharmacogenomics. The goal is to develop genetic signatures
that can be used to predict drug response and thereby
optimize drug therapy in order to ensure maximum efficacy
with minimal adverse effects.
breast cancer. The tests, a 21-gene test called Oncotype DX and a
70-gene test called MammaPrint, estimate the likelihood of cancer
recurrence at a distant site. Clinicians can use this information as
they decide whether anti-hormone treatment alone is likely to be
sufficient or whether a chemotherapeutic drug should also be used.
Although clinicians already use both tests, they are undergoing
further testing in clinical trials to help refine and expand their utility.
It is envisaged that near-term progress in genomic medicine should
yield additional clinically applicable gene signatures to guide
therapeutic decision-making and tailoring of a patient’s
from the drug. Breast cancer is a clear case in point. Women whose
breast cancers have a genetic alteration that leads to
overexpression of HER2 benefit from HER2-targeted therapies such
as trastuzumab and pertuzumab, as well as women whose breast
cancers express the estrogen and progesterone hormone
receptors, benefit from anti-hormone therapies. The 10% to 15% of
women, like Lori Redmer, whose breast cancers lack the
expression of HER2, the estrogen receptor and progesterone
receptor are said to have triple-negative breast cancer, and for
them there is no molecularly targeted therapy currently available.
A New Day for Genomic Medicine
The explosion of genetic information and our ever-increasing
understanding of how to apply it are providing patients with some
forms of cancer less toxic and more effective treatment options,
thereby realizing the promise of personalized medicine.
Many major advances are highlighted in this report, but gaps in our
knowledge remain. For example, there are many forms of cancer,
including liver and pancreatic cancers, for which we have
insufficient genetic and/or technical knowledge to design effective
molecularly targeted therapies. Even for those cancers for which
there is a therapy that precisely targets an underlying cancer-
driving molecular defect, not all patients’ cancers harbor the
matching molecular malfunction, so not all patients will benefit
Recent innovations have propelled rapid technological advances
that are making it possible to efficiently read every known
component of the DNA from an individual’s cancer. Capitalizing on
these advances is the goal of large-scale genomic enterprises such
as The Cancer Genome Atlas (TCGA) and the International Cancer
Genome Consortium (ICGC). These and other similar initiatives aim
to identify all of the genomic changes in many types of cancer, by
comparing the DNA in a patient’s normal tissue with the tumor
DNA, to discover the relevant genetic alterations that drive a given
cancer. This information can then be used to improve our ability to
diagnose, treat and prevent this devastating disease. In addition, it
promises to provide new avenues of precision treatments for
patients that currently have none. Moreover, near-term expansion
of the use of DNA sequencing will help uncover the mutations
specific to metastases, which are likely distinct from those in the
original tumors from which the metastases arise. Such analyses
have great potential to reveal new approaches to treating this
deadly stage of the disease where our current efforts fall short.
• Employs 1,800 people.
• 14,872 patient discharges and
240,361 outpatient visits.
• Diagnoses approximately 700 new
cancers per year, 200 of them being
• Provided net community benefits of
$27,481,152 between October 1, 2010
and September 30, 2011.
To date, large-scale genomic analyses have been completed for
just a few types of cancer, with research into many others
underway. The clear message that is emerging from these studies
is that while the genetic changes being uncovered vary widely,
taken together they affect only a handful of signaling networks.
Further, the same networks, albeit at different junctures, are
affected in different cancers (see Fig. 20, p. 70). This is changing
the way researchers view cancers. They see them more as genetic
diseases, defined not as much by where they originate—in the
breast, brain, lung, liver, etc.—but by the genetic changes that are
their Achilles’ heels (see Fig. 19, p. 67). At this juncture the major
challenge is to determine how to best use both our current
therapies and the newly developed drugs in combination to
American Association for Cancer Research