Researchers at the Stanford University School of Medicine are using tiny rings of DNA to induce cancer to reveal itself. Normally, clinicians search for biomarkers in blood and urine that cancers naturally excrete. This requires a separate test for each cancer type. But in the current research, the investigators developed the DNA rings that work by tricking cancer cells, but not normal cells, to produce a biomarker that can be easily detected.
The technique works with a variety of cancer types, activating a mechanism that produces secreted embryonic alkaline phosphatase (SEAP). This protein is normally produced by embryos, while it doesn’t exist in adults. The DNA rings have a sequence that effectively allows them to recognize when they’re inside a cancer cell. The rings also have the sequence coding for the SEAP protein. Once the ring recognizes it’s inside a cancer cell, it becomes activated and induces the cell to produce SEAP.
More details about the technology according to Stanford:
In front of the gene, the researchers inserted a short DNA sequence called a promoter. Promoters don’t code for protein production but, rather, are more like switches or rheostats telling the cell’s protein-manufacturing machinery whether and when to actually make the protein the gene codes for, and how much. Genes in every cell of all multicelled creatures are preceded by promoters. Although all of an individual’s cells contain precisely the same genes, how “on” the promoter is for a given gene in a given cell depends on varying local conditions within that particular cell at that particular time.
The particular promoter Gambhir and his colleagues snapped into the minicircle ahead of the SEAP gene normally regulates a gene called survivin that, in adults, is only “on” in cancer cells. So, in theory, the SEAP gene on the DNA minicircles Gambhir’s lab created would be produced only in cancer cells.
he survivin promoter has been used in gene-therapy experiments and is well-studied, Gambhir said. He noted that the survivin promoter is activated in a broad range of cancers, including breast, lung, ovarian and other major tumor types.
For the study, the researchers injected cells from human melanoma cell lines into laboratory mice. Ordinarily, a mouse’s immune system would attack any injected human cell, cancerous or not. But these mice were immune-compromised, and soon numerous tiny tumors started to develop throughout their bodies, especially in their lungs. Other mice of the same strain were given otherwise-identical injections that didn’t contain the cancer cells; they didn’t develop tumors.
About two weeks later, the animals’ blood was checked to make sure their baseline levels of SEAP were zero. Then the investigators injected the minicircles intravenously into the animals’ tail veins and measured SEAP levels in the mice’s 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.
Study in Proceedings of the National Academy of Sciences: Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker…
