Researchers seek to apply cancer gene advances

With the genetic understanding of cancer increasing at a rapid pace, scientists are exploring ways to link the information across the spectrum of care -- from initial screening tests to more tailored treatment options.

This concept was the theme of several presentations at last month's American Assn. for Cancer Research's first-ever international conference, "Molecular Diagnostics in Cancer Therapeutic Development: Maximizing Opportunities for Individualized Treatment," in Chicago.

"There are a great number of molecular technologies that impact every phase of cancer," said Richard M. Caprioli, PhD, one of the speakers and a professor of biochemistry at Vanderbilt University School of Medicine in Nashville, Tenn. "What we need to do is bring these technologies together."

On the screening end, numerous studies offered insights into how blood tests eventually could be used to refine currently problematic modalities, such as the prostate-specific antigen test. Researchers are trying to determine if human aspartyl (asparaginyl) beta-hydroxylase -- HAAH -- in blood is a better marker for prostate cancer than the PSA. PSA testing is widely used but controversial because of the false-positive rate. Most medical societies that issue related guidelines recommend offering it but have not come out in favor of making it routine.

According to a small study presented at the conference, HAAH was detected in the blood of 16 patients with this disease but not in the 23 who did not have it. Research is ongoing to determine how HAAH testing compares with that for PSA.

"We think that the specificity [of HAAH testing] is going to be higher," said William E. Gannon Jr., MD, vice president for clinical and medical affairs at Panacea Pharmaceuticals in Gaithersburg, Md., the company pursuing this possibility. "Initially, it will be an adjunct to PSA testing. But over time, it has the potential to replace it."

Researchers also are in search of detection tests for carcinomas such as lung cancer for which regular screening does not yet exist.

One such investigation focuses on whether levels of the cancer-specific protein tNOX in the blood are a possible early marker of this disease.

According to a paper presented at the meeting, when researchers tested for this substance, it was present in the blood of those with cancer and in seven out of the 65 smokers tested. Researchers are investigating whether these seven people actually have early-stage cancer.

Meanwhile, it was not detected among those individuals who did not have lung cancer or who were not smokers.

"This could be early enough that they might have a better chance of successful treatment," said D. James Morré, PhD, one of the paper's authors and a distinguished professor of medicinal chemistry at Purdue University in West Lafayette, Ind.

The need for a lung cancer screen is particularly acute, because it is one of the most prevalent cancers and causes a significant percentage of cancer-related deaths. A way to screen for it has proved elusive.

"We'd like to have a means of detecting lung cancer early in individuals who smoke with a low incidence of false-positives," said Dorothy Morré, PhD, study leader and professor of food and nutrition at Purdue.

Treatment potential

On the treatment end, researchers are looking for markers that will allow physicians to refine their choices and better predict their effects.

One study presented at the conference suggested that a single genetic assay can determine the best drugs to treat patients with gastrointestinal stromal tumors. Another study found that levels of the protein thymidylate synthase in colon cancer cells can indicate a patient's survival chances.

Researchers are particularly keen to use this kind of information to design clinical trials that test drugs in those most likely to benefit, either because of the patient's genetic make-up or the nature of the tumor, and least likely to be harmed.

"We know that some patients will have a good response and some will have a poor response or no response. And some will have toxicities," said Margaret R. Spitz, MD, MPH, professor and chair of the Epidemiology Dept. at the University of Texas-MD Anderson Cancer Center in Houston. "If we can predict who is most likely to get what, we hope to conduct faster, better and more humane clinical trials," she said.

Researchers stress, however, that while much of the research at this conference was promising, there was still more to be done before it reached patients.

"It's a huge work in progress," said Suzanne Miyamoto, PhD, a research biochemist at the University of California-Davis Cancer Center. She presented a paper on the use of serum glycan markers for the detection of ovarian, breast and prostate cancer. "We worry about false-negatives and false-positives. The tests need to be sensitive and robust."