America
India-born scientist's team develops blood test for early cancer detection
Washington, Feb 24
Researchers in the US, led
by an India-born physician scientist, have said they have developed a
new blood test that has the potential to detect cancers in their
earliest stages.
In a proof-of-principle study, researchers from
Stanford University, with Sanjiv Gambhir as the lead author,
administered a drug called DNA minicircles to mice and found mice with
tumours produced a substance that tumour-free mice did not make and was
easily detected 48 hours later in the blood.
The technique
"represents an alternative paradigm for improved cancer detection", said
the paper published in the US journal Proceedings of the National
Academy of Sciences Monday.
"If proven safe and effective, (it)
eventually may have potential as a powerful cancer-screening tool for
the general population," Xinhua news agency quoted the paper as stating.
The
hunt for cancer "biomarkers" in the blood, or substances that indicate a
probable tumour, is nothing new, but various tumour types naturally
secrete characteristic substances with each requiring its own separate
test, said Gambhir, chair of radiology and director of the Canary Center
at Stanford for Cancer Early Detection.
Complicating matters,
these substances are also quite often made in healthy tissues, so a
positive test result did not absolutely mean a person actually has
cancer. In addition, a tumour, especially a small one, simply may not
secrete enough of the trademark substance to be detectable.
Gambhir's
team found a way to force any of numerous tumour types to produce a
biomarker whose presence in the blood of mice unambiguously signifies
cancer, because none of the rodents' tissues would normally be making
it.
"This biomarker is a protein called secreted embryonic
alkaline phosphatase (SEAP)," they said in a statement. "SEAP is
naturally produced in human embryos as they form and develop, but it's
not present in adults."
To trick mice's cancer cells into making
SEAP and squirting it into the bloodstream, Gambhir and his colleagues
used a DNA minicircle, which is a tiny, artificial, single-stranded DNA
ring about 4,000 nucleotides in circumference, or roughly one-millionth
as long as the DNA strand that would result from stretching all 23
chromosomes of the human genome end to end.
They engineered the
DNA minicircle so that it can be activated by a particular promoter, a
short DNA sequence that only works in cancer cells. When activated, a
reporter gene on the minicircle will produce the protein called SEAP,
which can be detected in the bloodstream.
Then the researchers
injected the minicircles intravenously into mice bearing human melanoma
metastases and tumor-free mice and measured SEAP levels in the animals'
blood one, three, seven, 11 and 14 days later.
Within 48 hours,
SEAP was present in the blood of mice with tumours, but not in that of
the tumour-free animals. That signal began declining in strength as
early as 72 hours post-injection, fading to insignificance within the
next two weeks or so.
"Its maximum strength varied with the total
tumour volume in a mouse's lungs, suggesting that the test may be
sensitive not only to the presence of cancer but also to its extent,"
they said.
Although the minicircles were injected intravenously
to the mice in this study, it should eventually prove possible to
deliver them orally via a pill, Gambhir, born in Ambala, India, and a
recipient of numerous awards and honours, said.
"We haven't got
it down to a pill yet, but the oral delivery part of this is likely a
solvable problem -- only a few years off, not five or 10 years off," he
said, noting it would take much more time than that to prove that the
approach is safe to use in humans.