U.S. researchers develop new blood test for early cancer detection
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 tumors, but not in that of the tumor-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 tumor 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 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 will take much more time than that to prove that the approach is safe to use in humans.