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Biomarkers: How good a test are they?
October 2010
SHARING OPTIONS:
The boom in cancer biomarker investments in recent years has
not translated into major clinical success. Of the thousands of known
biomarkers (and counting), only a handful of them have actually made it into
the clinic.
In a recent issue of The Journal of the National Cancer
Institute, Dr. Eleftherios Diamandis,
professor of pathology and laboratory medicine at Mount Sinai Hospital in
Toronto and associate scientist at the hospital’s Samuel Lunenfeld Research
Institute, reports that no new major cancer biomarker has been approved for
clinical use for at least 25 years.
The last time a cancer biomarker was approved by the FDA was
in 2009.
However, that marker, the HE4 protein for ovarian cancer, was only
approved for monitoring recurrence and is thus an example of a “minor”
biomarker, he notes.
The reasons for biomarker failures include problems with
study design and interpretation, as well as statistical deficiencies, according
to Diamandis.
The National Institutes of Health defines a biomarker as “a
characteristic that is objectively measured and evaluated as an indicator of
normal biologic processes, pathogenic processes, or pharmacologic responses to
a therapeutic intervention.”
In the United States, one federal government program
alone—the Early Detection Research Network, which is devoted to finding
diagnostic cancer biomarkers—has spent “hundreds of millions” of dollars in a
10-year period, but has yet to yield a single FDA-approved marker, Diamandis
points out.
That’s not to say that there haven’t been any successes,
such as the protein HER-2, which is the target of the breast-cancer drug
Herceptin. HER-2, first discovered in the early 1980s, can be found on some
breast tissues and an excess of this protein is found in some forms of breast
cancer. Herceptin can act against HER-2 and, by looking for this biomarker in a
patient, doctors can work out who might benefit from Herceptin treatment.
Another example, the Philadelphia chromosome that results
from movement of DNA from one site on the human genome to another, is a marker
for chronic myeloid leukemia.
In an effort to understand why biomarker “breakthroughs”
have not made it to the clinic, Diamandis reviewed some biomarkers initially
hailed as breakthroughs and their subsequent failings.
“A biomarker must be released into circulation in easily
detectable amounts by a small asymptomatic tumor or its micro-environment; and
it should preferably be specific for the tissue of origin,” Diamandis notes.
“Also, if the biomarker is affected by a non-cancer disease, its utility for
cancer detection may be compromised. For example, the prostate-specific antigen
(PSA) biomarker, which is used to detect prostate cancer, is also elevated in
benign prostatic hyperplasia.”
Problems ranged from inappropriate statistical analysis to
biases in case patient and control subject selection.
“For example, the problems with EPCA-2 included reporting
values that were beyond the detection limit of the assay and using
inappropriate reagents to test EPCA-2, such as solid surfaces coated with
undiluted serum,” Diamandis reports.
Researchers are left to wonder just what the problem is with
these biological fingerprints and why are they proving so tough to use.
Moreover, Diamandis says one issue is that many of the molecules being
discovered are not specific to a single cancer.
“Levels of a protein called alpha-fetoprotein increase in
liver cancer, but can also rise in testicular or ovarian cancers,” Diamandis
points out. “Another protein, carcinoembryonic antigen, increases in colorectal
and pancreatic cancers, but is also raised by smoking.”
Diamandis concludes that “problems with pre-analytical,
analytical and post-analytical study design could lead to the generation of
data that could be highly misleading.”
While the lack of success can be disheartening, it may be a
little premature to just give up on the idea of biomarkers.
Adrian Ibrahim, associate director of Cancer Research Technology at
Cancer Research UK, tells the Guardian, “As new
technologies are developed ... we hope to see the development of more promising
cancer screening markers.” Code: E101029 Back  |
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