HMS professor devises single test for cancers

5 min read

Test tuned to individuals through genetic profiles

Imagine visiting a doctor’s office five years from now and, as a routine part of your annual physical, getting an accurate test that can tell whether you have cancer long before you have either symptoms or tumors detectable by other methods.

Such a test may be in the offing if early data from both laboratory mice and human cancer patients are an indication. A blood test invented by Professor of Radiology Amin I. Kassis, of Harvard Medical School and Brigham and Women’s Hospital, can detect several different types of cancer and, if early results hold true, do it more accurately than conventional tests at present.

In fact, if the results obtained thus far can be replicated, the findings have the potential to turn cancer screening and treatment on its head, making early detection – when chances for successful treatment are far higher – routine.

Kassis said that by using a different approach from current cancer tests, the new method avoids the problems of false positive and false negative results that complicate cancer diagnosis today.

“Currently, blood tests for cancer are, at best, not so good. All have high rates of false positives and false negatives,” Kassis said.

The test, which was described in a poster presentation Monday (April 20) at the annual meeting of the American Association for Cancer Research in Denver, has so far correctly detected the presence of four different types of cancer with 100 percent accuracy in laboratory mice and in seven cancer patients in which it’s been tried. Further, because the test relies on circulating tumor cells in the bloodstream, which are present once a solid tumor starts growing, it should be able to detect cancers early in their development, perhaps earlier and more accurately than they can be detected by current tests, Kassis said. That early detection aspect in humans has yet to be tried experimentally, however.

Blood tests for cancer today detect the levels of different markers in the bloodstream for different cancers. Not only are different tests required for each ailment, each person’s individual background level of the markers used is different.

The test for prostate cancer, for example, relies on the level of a protein called prostate specific antigen (PSA) in the bloodstream. PSA levels above a particular point are cause for action, but some individuals may have naturally low levels of that protein, meaning they can have the cancer and test negative. Others, meanwhile, may have naturally high levels of PSA, meaning they might not have the disease and still test positive. Environmental variables can also affect the outcome of the test. According to statistics from the Centers for Disease Control and Prevention, out of 15 men over age 50 who test positive for high levels of PSA, only three will actually have prostate cancer.

The new test relies on the byproducts of the death of circulating tumor cells, which are shed into the blood by even very small tumors regardless of whether or not they have metastasized, or spread throughout the body. These circulating cells are abundant, with 1 million to 5 million in the bloodstream for each gram of the tumor’s size. Most circulating tumor cells normally die on their own and are cleared from the body by certain white blood cells, which engulf the cell’s remnants.

The test compares two types of cells that can be extracted from a patient’s blood. One is a kind of white blood cell called a phagocyte. If the patient has cancer, the phagocyte would have markers for that cancer from the bits of circulating tumor cell it has ingested. The second is a cell closely related to a phagocyte that provides a genetic baseline for that particular patient against which to compare the results.

Using a cell-sorting machine, fluorescently labeled antibodies, and a gene chip with an array of markers for different cancers, Kassis said detecting cancer is relatively straightforward.

“The one that lights up tells you that the patient or mouse has cancer, and which cancer it is,” Kassis said.

After trying out the test on mice, Kassis recently tried it out on human volunteers who were known to have cancer. So far it has been 100 percent effective in detecting cancer in every human and animal on whom it has been tried.

“Not only did it work, it worked way beyond our expectations,” Kassis said. “We are totally shocked. When you get an idea, it often sounds right, but nature has its own angles.”

The idea for the test came to Kassis four years ago when he was attending a talk on circulating tumor cells. Though his specialty today is using radiation in the diagnosis, imaging, and treatment of cancer, the talk touched on topics with which he was familiar from his doctoral work in immunology at McGill University in Canada during the mid-1970s.

He put the idea aside for two years until a summer intern in Kassis’ lab, John-Paul Chilazi, was looking for a project. Kassis set him to work on the idea. Though the intern left after a few months, Kassis and S. James Adelstein, Cabot Distinguished Professor of Medical Biophysics and professor of radiology; Jochen H. Lorch, instructor in medicine at the Dana-Farber Cancer Institute; and research fellows Pichumani Balagurumoorthy and Stephen Stribbling continued working on it.

Kassis, who is director of the Radiobiology and Experimental Radionuclide Therapy Section of the Laboratory for Experimental Nuclear Medicine, has continued developing the test, on which Harvard has filed U.S. and world patents. Further progress is dependent on funding, he said, but with the needed research money and continued promising results, the test might be ready in five years.

Kassis said the approach is an example of the increasing personalization of medicine and envisions the test being routinely available in labs, to be used for both screening and follow-up after treatment.