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Science closing in on tests for 'stealth' cancers

By E. J. Mundell

NEW YORK, May 18 (Reuters Health) - Imagine a disease that arises

slowly over months or years, without symptoms, until the sudden onset

of acute illness. Now imagine being told by your doctor that the

disease is already too far advanced to be treated with surgery or

medication, and that death may come within months or even weeks.

That scenario is a grim reality for the great majority of the nearly

54,000 Americans diagnosed every year with hard-to-detect pancreatic

or ovarian cancers, cancers for which an accurate early-detection

test may be essential to patient survival.

Now, researchers searching for just these kinds of tests say they are

close to achieving their goal.

In fact, a blood screen for pre-symptomatic ovarian cancer is

currently in clinical trials, and may be " commercially available

within a year, " according to Dr. Fishman, director of the

National Ovarian Cancer Early Detection Program at Northwestern

University Medical School in ton, Illinois.

" That's just the tip of the iceberg, " Fishman added. " We have much

more powerful tests coming out right now. "

Ovarian cancer--the fifth-leading cancer killer for women--has long

been one of the most feared cancer diagnoses. Because the ovaries are

small organs located deep within the abdomen, " by the time you have

symptoms [the cancer] is really widespread, " Fishman explained. Of

the more than 25,000 women diagnosed with ovarian tumors each

year, " at best, about 15%...will be alive five years later, " he said.

" So of the cancers a woman can have, this is probably one of the most

lethal, if not the most lethal. That's why early detection is so

important. "

In collaboration with researchers around the world, and with a grant

from the National Institutes of Health, Fishman's team is homing in

on blood markers specific to ovarian tumors. One such marker, called

lysophosphatidic acid (LPA), appears to be produced at higher levels

in women with ovarian cancer versus those without the disease. LPA is

the marker currently in clinical trials, a necessary step for

approval by the US Food and Drug Administration (FDA).

Research is also ongoing in the fight for an early detection test for

the fourth-leading cancer killer of both men and women--pancreatic

cancer. While the number of Americans diagnosed with pancreatic

cancer every year is comparatively small (29,000 compared with nearly

180,000 cases of either prostate or breast cancer), the disease

has " a 99% mortality rate--the highest mortality of any cancer, "

according to Fleshman, executive director of the pancreatic

cancer patient advocacy group, PanCan (www.pancreaticcancer.org).

" The average life expectancy after diagnosis is just 3 to 6 months, "

Fleshman added, with just 4% of patients living 5 years after

diagnosis.

Because pancreatic tumors tend to evolve into very aggressive cancers

at a relatively early stage in their growth, cancers originating in

the pancreas have almost always spread to adjacent organs by the time

physical symptoms (usually back pain or jaundice) occur. Surgery is

usually not an option at this point, nor is chemotherapy.

Fleshman, who lost her father to the disease, said that most patients

and their loved ones react with a " disbelief that there is nothing

that anyone can do to help you. You're madly searching for something

out there, and then all of a sudden, it's over. "

However, researchers at s Hopkins University in Baltimore,

land, may be closing in on an early detection test for this

cancer as well.

" We're looking at genes that are expressed in the cancer, " explained

lead researcher Dr. Goggins. With funding from the National

Cancer Institute, Goggins' team is currently examining a range of

possible candidates, hoping to spot proteins produced by aberrant

genes that could prove to be highly specific blood markers for pre-

symptomatic pancreatic cancer.

Even more promising may be markers based on DNA methylation, a

molecular process that acts like a switch turning genes " on "

and " off. "

" Cancers learn ways to screw up methylation in cells, " Goggins

explained, and " there will be some [markers] that will be specific to

[pancreatic] cancer. " Methylation-based markers might best be tested

in stool, or pancreatic secretions, rather than blood, he said.

One roadblock facing research into highly accurate early-detection

tests is the need to minimize 'false positive' test results, since

more than one condition may prompt levels of a specific blood or

stool marker to rise or fall. But Goggins remains optimistic.

" I would think that over the next couple of years we will establish

better diagnostic tests, " he said, " and through the next 3 to 5 years

we'll generate a panel [of markers] that could be useful in clinical

trials. "

Researchers say accurate early-detection tests would be most helpful

in screening patients who have a genetic or physiological

predisposition to hard-to-spot cancers. But the ideal would be tests

accurate enough to be used as a routine screen by the population at

large, in the same way that annual PSA testing for prostate cancer is

advised for men older than 55.

Developing these tests costs money, of course, and everyone agrees

that current research efforts are woefully under-funded. Ironically,

part of the problem lies in the very lethal nature of ovarian and

pancreatic cancers. " Whereas with breast cancer you've got a whole

lot of survivors out there fighting for the cause, we don't have that

same thing, " PanCan's Fleshman explained.

" What we could use in our program is someone like a Trump, "

joked Northwestern's Fishman, who believes much more money needs to

be directed to the search for an ovarian cancer test.

In the meantime, PanCan--formed just 2 years ago--is busy lobbying

Capitol Hill for " its share of the pie, " according to Fleshman. She

remains hopeful that more money will soon be made available for

research. " We're laying down the right track, " she said, " but we're

starting from ground zero. "

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