NEW YORK(GenomeWeb) – Leveraging technology from the University of Bradford, a UK firm is developing a blood-based screening test for cancer that could reduce the number of unnecessary biopsies and other procedures.
Called the Lymphocyte Genome Sensitivity Test, the technology uses UVA light to differentiate patients who have cancer from those who don't based on their DNA. Oncascan was founded three years ago in order to move the LGS test to the commercialization stage, and the company is currently validating the technology. It also is exploring ways to make the test more automated, and any commercial launch of the technology remains "several years" away, its Managing Director William Finch told GenomeWeb in a recent interview.
If successful, though, Oncascan officials believe it could significantly reduce the number of biopsies and other procedures performed on patients who may be suspected of having certain types of cancer, but who later are found to be healthy.
The technology cannot tell a physician the specific type of cancer someone may have. Instead, Oncascan envisions LGS as an opt-out screening tool for specific cancers in order to steer patients away from unnecessary procedures that could be unpleasant, or pose health risks, and are costly to patients and the healthcare system.
The focus for the moment is on bowel and prostate cancer, "because we believe that there is a good economic case for using the test to screen out the large number of false positive cases going to biopsy," Finch said.
In the case of bowel cancer in the UK, for example, about 7 percent of patients suspected of having bowel cancer will actually have the disease, while approximately 23 percent will have polyps that need to be removed, he said. The remaining 70 percent of patients don't have cancer or pre-cancerous polyps and don't need any kind of intervention. Nonetheless, they may be directed to a procedure, usually a colonoscopy, because the initial test results are too ambiguous to determine whether the patient may or may not have cancer.
"What we want to do is to say of the 70 percent who didn't need colonoscopy, how many could we have predicted and sent home without having had the investigation," Finch said. Longer term, Oncascan plans to investigate the utility of LGS for lung and breast cancer, he added.
While Oncascan suspects the technology may have broad utility for many cancers and possible use as a general cancer screening tool, the company has not yet conclusively validated that capability, Finch said. Furthermore, even with broad coverage, the test would have very little use for a doctor if it cannot specify what cancer a patient may have, he acknowledged.
"It might ultimately be accepted for that role, but initially we want to focus on the very clear-cut benefit of reduced biopsies," he told GenomeWeb.
Shedding light on cancer with UVA
The LGS technology was developed at the University of Bradford by a team of researchers led by Diana Anderson, a professor of biomedical science. Working on the idea that white blood cells are under stress when a person has cancer, they set about determining whether something could be measured if the white blood cells were exposed to additional stress from UVA lighting, she said in a statement from the university.
"We found that people with cancer have DNA which is more easily damaged by ultraviolet light than other people. So the test shows the sensitivity to damage of all the DNA — the genome in a cell," she said.
Anderson and her colleagues' work are described in a study published online in July in The FASEB Journal.
The LGS technology works as follows: Cells are lysed and run through an electrophoresis gel and stained for DNA. Cells that have DNA damage will unravel and take on the appearance in the electrophoresis field of a comet streaking across a night sky, Finch said. Most of the DNA will be concentrated in the nucleus of the comet, but some will stream out of the tail.
"The more damage you have, the more it streams out, and you can quantify that" by determining something known as an olive tail moment — the product of the tail length and the fraction of total DNA in the tail — Finch said.
The method developed by Anderson and her colleagues acts as something of a stress test for the DNA whereby UV light is given in small amounts, he said. Other research has demonstrated that patients with cancer have DNA that is less stable when it is exposed to radiation that is more intense than UV light, such as gamma radiation. The problem with gamma radiation, of course, is that the intensity of the radiation is too high for it to be used for diagnostic purposes.
But if the form of radiation used is not intense enough, the results may not be able to differentiate cancer from non-cancer in a patient.
"And we think we've got to the point where we can emphasize the difference between" cancer and non-cancer, Finch said.
In The FASEB Journal study looking at colon cancer, melanoma, and lung cancer, Anderson and her co-researchers found a correlation between the length of the comet tail and the DNA damage and patients who were ultimately diagnosed with cancer, those who were diagnosed with pre-cancer, and those who were healthy.
The results are still early and additional research needs to be done, Anderson said in a statement, but "[w]hilst the numbers of people we tested are, in epidemiological terms, quite small, in molecular epidemiological terms, the results are powerful." A total of 208 healthy patients and patients with cancer participated in the study.
"We've identified significant differences between the healthy volunteers, suspected cancer patients and confirmed cancer patients of mixed ages at a significant level of P<.001," meaning the possibility that the results of the study were due to chance is one in 1,000. "We believe that this confirms the test's potential as a diagnostic tool," she added.
Finch said that the LGS technology may also have use for monitoring cancer patients who have been treated with therapy. In the case of bowel cancer, he said, the method would offer a cheaper alternative to cytoscopy.
Oncascan is currently involved in a clinical trial at the Bradford Royal Infirmary to validate the technology and gather more data to show that in a working clinic it will be able to identify those patients who need further treatment/evaluation.
"We have to do more … evaluations to show that this is a reliable test, but so far we get remarkable separation between normal and not healthy people," Finch said.
Another startup, however, may already have a leg up on Oncascan in the development and commercialization of a general cancer screening test. Miroculus has developed a technology platform it calls Miriam that detects miRNA in blood using a 96-well format. Results can be achieved in about 90 minutes.
Miroculus did not respond to requests for an interview, but according to its website, Miriam uses proprietary chemistry to detect specific miRNA associated with cancer. When the miRNA is present, the wells glow, and by analyzing the intensity of the glow, Miriam can tell which miRNAs are present in the sample and whether they are downregulated or upregulated.
Additionally, researchers at Japan's National Cancer Center are developing an miRNA-based test that would be able to detect more than one dozen cancers. That project is expected to last five years.
Oncascan's technology is also some years from commercialization, if it ever reaches that stage. Along with validation of the technology, work is underway to make it more user-friendly. Anderson and her colleagues had begun exploring the commercial potential of their research, but Finch and his business partner David Squire took over those efforts and licensed the technology with an eye toward automating it.
The current method can be done in a lab, and while Finch said that there is nothing "particularly unusual" about the technique, it is "quite laborious and quite drawn out" and would need to be made into at a semi-automated instrument for it to have commercial value.
Oncascan's focus now is on making the method "more controlled, reproducible, and faster" so that the hands-on time is minimized. To that end, Oncascan has made a few adjustments to the technique, including the use of whole blood, which would eliminate the separation step. There are no plans currently to develop its technology as an LDT, he added.