Tailoring cancer treatments

Researchers believe the test will give doctors a way to tailor cancer treatments to individual patients by monitoring how well their tumour has responded to surgery or therapy. In principle, the test could be used to keep watch over any kind of cancer that scientists can collect cells from.

Scientists developed the test after deciphering the full genomes of tumour tissue taken from six patients. Most cancers contain large-scale rearrangements of genetic material that aren’t seen in healthy tissue, so they can be used as a genetic “fingerprint” for the tumour. A patient who has recently been diagnosed with cancer will have high levels of a tumour’s genetic fingerprint in their blood, because cancers shed cells and DNA into the bloodstream.

When a cancer is operated on or treated with radio- or chemotherapy, the levels of the fingerprint should fall, and vanish altogether if the tumour has been eradicated.
A team led by Victor Velculescu, professor of oncology at Johns Hopkins University in Baltimore, developed individual tests for six patients, four of whom had bowel cancer and two breast cancer.

Genetic tests on one patient with bowel cancer, for example, revealed that a chunk of one chromosome in the tumour had fused with another chromosome. This huge genetic glitch or “biomarker” was a major part of the tumour’s genetic fingerprint.
Doctors found that after surgery, levels of the biomarker dropped in the patient, but then rose again, suggesting the cancer remained in their body. After chemotherapy and further surgery, the biomarker levels dropped substantially but not to zero. The residual level of cancer was traced back to a tumour that had spread to the patient’s liver.
Scientists liken the technique to “searching for the genetic breadcrumb trail left by lingering cancer cells after surgery or during drug therapy.”

The test, known as personalised analysis of rearranged ends (Pare), could potentially be developed for any kind of cancer, according to Velculescu. “There is currently no test for cancer patients that provides personalised biomarkers for clinical management of disease,” he said.

Reading the full genome of a patient’s cancer currently costs around £3,200, but the price of the technology is falling rapidly as it improves. The researchers believe the Pare test will eventually be more cost-effective than standard hospital CT (computerised tomography) scans, which are less able to detect microscopic cancers.
The test relies on identifying rearrangements of large chunks of DNA rather than single-letter changes in the genetic code, which are more difficult to spot. “These alterations, like the re-ordering of chapters of a book, are easier to identify and detect in the blood than single-letter changes,” said Bert Vogelstein, a co-author on the study.