These genes were also found to promote the spread of breast cancer to the lungs. The study, conducted in mice and reported in this week's Nature, helps to explain how cancer metastasis can occur and highlights targets for therapeutic treatment.

Metastasis, the leading cause of mortality in cancer patients, entails numerous biological functions that collectively enable cancerous cells from a primary site to disseminate and overtake distant organs. A number of genes are already known to contribute to the spread of breast cancer cells to the lungs.

Using genetic and pharmacological approaches, Joan Massagu, PhD, Chair of MSKCC's Cancer Biology and Genetics Program and a Howard Hughes Medical Institute Investigator, and colleagues showed how four genes facilitate the formation of new tumor blood vessels, the release of cancer cells into the bloodstream, and the penetration of tumor cells from the bloodstream into the lung. The gene set comprises EREG (an epidermal growth factor receptor ligand), the cyclooxygenase COX2, and MMP1 and MMP2 (matrix enzymes that are expressed in human breast cancer cells).

The researchers conclude that drug combinations that target one or more of the proteins encoded by these genes may prove useful for treating metastatic breast cancer.

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"Among other things, the study has the potential to improve our understanding of early ovarian cancer," Cho says. "In the last 30 years, we haven't done a lot to improve the overall survival of ovarian cancer patients."

Women and their doctors at present have no effective ways to detect ovarian cancer at an early, treatable stage. There are few if any early physical symptoms of ovarian cancer and no tests to detect cellular changes that might indicate precancerous lesions, as Pap smears do for cervical cancer. By the time a woman with ovarian cancer experiences symptoms, tumors are typically large and often metastatic.

Standard therapy for ovarian cancer now usually involves surgery to remove the tumor, followed by chemotherapy, which is initially effective but not curative. The disease frequently comes back in a drug-resistant form. New drugs are badly needed that can target the distinct molecular defects in the different types of ovarian cancer, which may be more accurately seen as not one disease, but several related ones.

Next, Cho plans to tackle the "very big challenge" of dissecting the molecular basis of serous ovarian cancer, the most common form of ovarian cancer and the one responsible for most ovarian cancer deaths.

That work, combined with ongoing projects on ovarian endometrioid adenocarcinoma, could help researchers develop screening tests that can detect the most common types of ovarian cancer early, and design more effective treatments for women with advanced disease.

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