Searching for less invasive screening tests for cancer, Johns Hopkins
scientists have discovered proteins present in blood that accurately
identify colon cancer and precancerous polyps.
Initial studies of the proteins, CCSA-3 and CCSA-4, suggest they
could be used to develop a blood test to identify at-risk individuals.
“The reality is that many people are not getting regular screening
colonoscopies,” says cancer researcher Robert Getzenberg, Ph.D. “So,
ideally we’d like to identify those with some molecular for the
disease and really need them.”
Current screening guidelines for healthy people call for a baseline
colonoscopy – colonic cleansing, fasting and heavy sedation followed
by the insertion of a flexible, optical-scanning scope through the
rectum into the colon — at age 50, followed by re-screening at least
every five to 10 years. Colonoscopy is not foolproof; cancers can
develop between screenings.
First discovered by Getzenberg and colleagues at the University of
Pittsburgh through a protein scan, the two blood-dwelling proteins
are thought to be remnants of cellular debris castoff from dead
cancer cells. Although the proteins’ roles are not entirely clear,
the Johns Hopkins scientists say they are part of the scaffolding
that supports structures within a cell’s control center, the nucleus.
Alteration of such nuclear scaffolding is a hallmark of cancer cells
that is easily detectable under the microscope as a misshapen and
discolored nucleus. That led Getzenberg to the notion that “there
must be something at the molecular level that would form a molecular
flag for cancer via a blood test.”
To find the flag, Getzenberg’s team drew blood samples from 107
apparently healthy individuals the day before their scheduled
colonoscopies, and from 28 colorectal cancer patients.
Using a particular concentration of scaffold-proteins as a marker for
disease, the Johns Hopkins team – which did not know the colonoscopy
results in advance — were 100 percent accurate in identifying the 28
existing cancers. Using the same protein markers, investigators also
correctly identified 51 of 53 individuals (96.2 percent) with normal
colons and 14 of 18 (77.8 percent) people with advanced precancerous
polyps, which Getzenberg says are the most important to detect
through routine screening.
When researchers combined samples, they correctly identified 42 of 46
(91.3 percent) containing both cancers and advanced precancerous
polyps. Protein levels were accurate in correctly assessing
additional blood samples from 125 people with benign conditions and
other cancers.
“These proteins seem very good at separating normal samples from
cancerous ones and identifying other groups with pre-cancers at high
risk for disease as well,” says Getzenberg, who is a professor of
urology and director of research at Johns Hopkins’ Brady Urological
Institute. Results are published in the June 15 issue of Cancer Research.
The researchers are planning larger studies at several hospitals over
the next several months. It may take several years to complete the
full range of testing.
Getzenberg says that storing and processing the samples are among the
major hurdles in biomarker development, a field that spans ongoing
research on many cancers and various body fluids. “It is difficult to
get many facilities to adhere to precise storage and processing
conditions important for keeping proteins stable,” he says.
“Different conditions could create incorrect results.” Researchers
also differ in the type of biomarkers they seek, with some looking
for proteins, like Getzenberg, and others searching for DNA components.
Getzenberg and the University of Pittsburgh hold a patent for the
technology described above, which is licensed to Onconome
Inc. Funding for the study described in this article was provided by
Onconome Inc. and the National Cancer Institute. Under a licensing
agreement between Onconome Inc. and University of Pittsburgh,
Getzenberg is entitled to a share of royalty received by the
University on sales of products described in this article. Getzenberg
also is a paid consultant to Onconome Inc. which has a licensing
agreement with The Johns Hopkins University covering CCSA-3 and -4
related technologies. The terms of this arrangement are being managed
by The Johns Hopkins University in accordance with its conflict of
interest policies.
Additional authors are Eddy S. Leman, Grant W. Cannon, Lori J.
Sokoll, and Daniel W. Chan at Johns Hopkins; and Robert E. Schoen and
Joel L. Weissfeld at the University of Pittsburgh Cancer Institute.
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