Vulnerable to Anti-Angiogenic Drugs

In a study the investigators estimate that the subtype may account for a third of all serous ovarian cancers, a common cancer of the surface of the ovaries. The discovery of the subtype, made by analysing data from the clinical records of more than 1,500 serous ovarian cancer patients and samples of their tumours, may spur clinical trials to determine if patients with the subtype can benefit from anti-angiogenic therapies now being tested in other cancers.

"Unlike breast cancer, where we can distinguish different subtypes based on their genetic signatures, ovarian cancer has been viewed as a monolithically homogenous disease – each tumour very much like every other," says Doctor John Quackenbush with his colleague Doctor Ursula Matulonis "With this study, we have shown that serous ovarian cancer exists in at least one distinct subtype at the molecular level, raising the possibility that it will be vulnerable to therapies directed at its molecular weaknesses."

Ovarian cancer is the fifth leading cause of cancer death for women in the United States, responsible for more than 15,000 deaths annually in this country, according to the American Cancer Society. High grade serous ovarian cancers – the focus of the current study – are one of several varieties of tumours that appear in the "epithelial" tissue lining the ovaries. Epithelial tumours account for about half of all ovarian cancers.

In the current study, researchers scanned the activity of thousands of genes in high grade serous ovarian cancers from 129 patients with an advanced stage of the disease. They then sifted the data using an algorithm called rISIS, which randomly assigns the tumour samples to different groups until it finds a grouping with a distinct set of genetic characteristics. That grouping represents a potential cancer subtype.

The technique yielded four possible subtypes of high grade serous ovarian cancer, but only one of them held up when researchers applied a different technique for scanning gene activity. When researchers catalogued the genes that were particularly active – or "highly expressed" – in that single subtype, a key trend appeared: many of the genes were known to be involved in angiogenesis, the process by which tumours build blood vessels to tap into the bloodstream for oxygen and nutrients. This distinctive array of overactive genes was dubbed the "angiogenesis signature."

"The analysis confirmed our finding," Quackenbush relates. "The angiogenic subtype is real." When investigators analysed the medical records of those 1,606 patients, they found that those with the angiogenic subtype tended to have more advanced, aggressive tumours than those without the subtype.

MEDICA.de; Source: Dana-Farber Cancer Institute