Cancer detectors more sophisticated

By: BRADLEY J. FIKES - Staff Writer | Saturday, January 13, 2007 7:05 PM PST ∞

The more we learn about cancer, the more confusing it can seem. Cancer isn't a single disease, but a family of diseases that vary greatly in their danger, which tissues they attack and how they're caused.

Cancer drugs hailed as precisely targeted "magic bullets" ran into this messy reality. Cancer cells are not like sneaky, disciplined infiltrators. They're more like disorganized mobs running every which way, with a few lucky members always managing to avoid capture.

At last, increasingly sophisticated cancer tests, many relying on new knowledge of how genes work, are reaching doctors' offices to run down these outlaws. In addition to detecting tumors, the tests can determine the type of cancers, what kind of threat they pose, the best methods to treat them, and monitor the results of treatment. The newer tests also detect the biochemistry of patients, allowing predictions of how they will tolerate cancer medications.

Getting the knowledge from laboratories to doctors may be a problem, however. The newest tests, which have greatly expanded doctors' ability to track the "history" of individual tumors, tend to be expensive. Some of the most advanced, based on the so-called "gene chips," have not been approved for reimbursement by health insurance companies. Here's a snapshot of this changing landscape.

Taking a look

The oldest way of finding a cancer is with the eyes: the doctor examines a suspicious lump or change in skin complexion. Computerized tomography (CT) imaging, a more precise form of conventional X-ray technology, looks beneath the surface to spot changes invisible to the eye. Newer machines such as PET (positron emission tomography) enable doctors to look for signs of abnormal cellular metabolism.

"Most tumors love to eat up glucose because they are hypermetabolic," said Dr. Allen Nalbandian, a radiologist at Valley Radiology Consultants in Escondido. Tumors need that energy to grow and to metastasize, he said. So patients are given glucose "tagged" with a radioisotope. Cancer cells gobble up this radioisotope, producing "hot spots."

The latest advance is to marry CT and PET testing in a single machine, Nalbandian said. The PET detection of a "hot spot" indicative of cancer is overlaid onto a CT map of the body to mark the cancer's location. These functions used to be done with separate tests, Nalbandian said, but combining them into one machine makes location of the tumor more precise. The combined machine can detect tumors as small as 1 centimeter.

"It's the hottest trend now" in cancer imaging, said Nalbandian, who also practices at Palomar Pomerado Health. The hospital system plans to get a CT/PET scanner later this year, he said, and they are already in use at other locations in the county.

These combo scanners are also useful in tracking how tumors respond to treatment, Nalbandian said.

Up close

However, many cancers can't be easily detected by large-scale imaging. This is particularly true of "liquid" tumors such as lymphomas, cancers of white blood cells.

So companies like Genoptix examine blood samples for signs of cancer. These include characteristically misshapen cells, deformed chromosomes, and genetic markers associated with cancer-causing mutations. Genoptix, based in Carlsbad, performs these tests to help oncologists plan treatment that matches the individual "history" and characteristics of each patient's cancer.

CellSearch, one of the newest tests Genoptix offers, was approved last summer by the U.S. Food and Drug Administration. Developed by a Johnson & Johnson subsidiary, the test examines circulating tumor cells in metastatic breast cancer.

The test is so sensitive it can detect one tumor cell out of 20 million cells in a blood sample, said Dr. Mike Nerenberg, medical director and vice president of medical affairs. CellSearch can detect more quickly than a CT scan if a cancer treatment is working, Nerenberg said. With a CT scan, it can take 12 weeks to tell if a tumor is shrinking under the treatment or not.

"Why give a woman three cycles of chemotherapy over three months if you can tell after one cycle if the treatment is working?" Nerenberg said. "Conversely, (CellSearch) can reassure a woman that the treatment is working, even if there are some side effects, encouraging her to go on with it."

That determination is made by a count of tumor cells. If the count goes down in successive tests, the cancer is being brought under control. If the count goes up, the treatment is not working.

If all goes well, CellSearch's approved uses will be expanded later this year to prostate and gastrointestinal cancers, Nerenberg said.

The appearance of tumor chromosomes can be predictive of how dangerous the cancer is. This examination is called karyotyping. For example, chronic myleogenous leukemia, or CML, displays a characteristic "translocation," or exchange, between chromosomes 9 and 22. If caught in its early stages, CML responds exceptionally well to a drug called Gleevec, with nearly complete success in eradicating the cancer, Nerenberg said.

But if not caught early, CML cells accumulate more changes and become harder to treat.

Drug susceptibility testing for cancer drugs are coming into greater use. These tests determine how well a patient can tolerate a cancer drug. One test now available measures the potential reaction of a patient to irinotecan, used to treat colorectal cancer. Some patients can't metabolize it well, Nerenberg said, and if given a standard dose they may develop a potentially fatal bloody diarrhea. Such patients might be given another cancer drug, or a lower dose of irinotecan.

About a half-dozen of these tests are now available, and more are on the way.

"There are a bunch of ones on the launching pad, but the FDA hasn't given its stamp of approval yet," Nerenberg said.

In the genes

All cancers are genetic in origin, caused when cells acquire a series of mutations that allow them to grow uncontrollably. Some people inherit genes that are already partially mutated along one of the paths to cancer, placing them at higher risk. In other cases, the mutations occur entirely over the lifetime of the person who develops cancer. Certain factors, such as exposure to cigarette smoke, are known to encourage cancer-causing mutations.

Tests for mutated cancer genes, or "oncogenes," have been around for years. But since there are many genes involved in developing cancer, the presence of one usually isn't a firm diagnosis. The more genes tested, the better.

The most advanced form of genetic testing is now performed on "gene chips," or "microarrays." These are semiconductor chips linked to sequences of oligonucleotides, segments of DNA or RNA. The cancer microarrays are constructed with specific oligonucleotides that adhere to oligonucleotides found in genetic mutations known to be associated with cancer or precancerous mutations.

"Microarrays are a significant advance both because they may contain a very large number of genes and because of their small size," according to a primer by the National Institutes of Health. "Microarrays are therefore useful when one wants to survey a large number of genes quickly or when the sample to be studied is small."

The primer is available at tinyurl.com/wn3wq.

While these microarray tests have been proven accurate, Nerenberg said they're not yet generally available to the public. That's mainly because they're not reimbursed by health insurance.

"Physicians are struggling to use them," Nerenberg said. "One, they don't get paid by the insurance companies, and two, it's just a little too early."

Thinking ahead

The cancer tests described above are usually given when there's already reason to suspect a person has cancer. But there are also a number of tests that people should have when they get older, even if they feel perfectly healthy. These include exams for breast, colon and prostate cancer, said Dr. Alberto Bessudo, an oncologist who practices in Vista and Encinitas at San Diego Pacific Oncology & Hematology Associates Inc.

Upon reaching 40 to 45, everyone should have a colonoscopy, Bessudo said. This can be done directly, with an instrument called a colonoscope inserted through rectum. A less invasive alternative is "virtual colonoscopy," in which a CT scan is performed on the colon. The colon must still be inflated with air, however.

Women over 40 should have an annual mammogram, a form of x-ray performed on the breast.

Men over the age of 45 should have a digital rectal exam, in which the prostate is palpated by the doctor through the rectum. After that, men should have an annual PSA (prostate-specific antigen) blood test. This measures the level of a chemical that is typically elevated in those with prostate cancers.

Family history also comes into play, Bessudo said. Those with relatives who have had breast, colon, prostate or ovarian cancer need to tell their doctors. They will be more closely monitored.

Women with cancer-causing mutations of genes called BRCA-1 and BRCA-2 may be advised to have their breasts or ovaries removed. If they don't want to do that, perhaps because they intend to have children, they should get more frequent checkups and be especially alert to any warning signs, Bessudo said.

Contact staff writer Bradley J. Fikes at (760) 739-6641 or bfikes@nctimes.com.

Find, fight cancer in one pass

One day, tumors might one day be detected and treated at the same time, according to new research by La Jolla scientists in the emerging technology of "homing nanoparticles." Although still far from use in patients, the nanoparticles have been used in animals to locate tumors and reduce their blood supply.

The nanoparticle technology has been under development for years by a team of scientists from the Burnham Institute for Medical Research, UC San Diego and MIT. They published a paper in the Proceedings of the National Academy of Sciences detailing their findings.

Ultra-small particles, made out of a form of iron oxide now used as MRI contrast agents, were affixed with a protein that binds to clotted blood, found in solid tumors. The molecules homed into the tiny blood clots, shutting down as much as 20 percent of blood vessels in the tumors. This is not enough to reduce tumor growth, the researchers concede, but they say it's a promising start.

More information about homing nanoparticles is available at tinyurl.com/t9tzv.

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