Metastatic ovarian cancer

The growth factor lysophosphatidic acid (LPA) is emerging as a key player in the cascade of events that lead to metastatic ovarian cancer, Dr. Fishman said.

"It's intraabdominal disease that kills," he said, emphasizing that numerous processes have to fall into place for cells to migrate, adhere to a distant site, invade, and proliferate.

"You can't shut down cancer by attacking one" element, he said. "Tumor cells are very clever."

Stymied on one front, they seek alternatives. Seemingly captured, they escape.

But it turns out that LPA fulfills so many stimulatory functions that targeting it has the potential of substantially crippling the metastatic process, Dr. Fishman predicted.

"This lysophospholipid pretty much does every bad thing you can think of. It stimulates every bad process that helps the cancer to grow," he said.

It upregulates proteinase activity, triggering movement of enzymes to the cell surface; organizes and directs tumor cells; stimulates cell proliferation; and makes cell membranes more fluid, thus allowing tumor cells to "squeeze through the tight walls of the cell matrix."

At distant sites, LPA stimulates cellular adhesion, binding ability, chemotaxis, and vesicle formation.

It inhibits apoptosis and affects Fas ligand expression, essentially instructing tumor cells to tell natural killer cells, "You're supposed to die. I'm fine," Dr. Fishman said.

Because LPA is integrally involved in tumor cell-specific motility, the possibility exists that it could be targeted by chemotherapy that would spare healthy cells, he added.

Importantly, LPA is also elevated in the blood of patients with ovarian cancer, including those with early-stage disease.

In a study, it was far more accurate than CA 125 in signaling the presence of stage I disease.

Among 97 plasma samples from women with stage I disease, CA 125 accurately identified just 22. But 90 of 97 samples were identified as coming from women with stage I disease by a complex LPA assay.

The CA 125 test picked up 18 of 30 samples from patients with stage II ovarian cancer and 120 of 145 of those from patients with stage III disease. But LPA identified ovarian cancer in all 30 samples from patients with stage II disease and all 145 samples from those with stage III cancer.

Dr. Fishman noted that testing for LPA is expensive and "not an easy assay" to perform because it uses Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LCMS-MS) technology.

Research is underway, however, to try to maximize its utility as part of a multipronged paradigm to better identify early-stage disease.