Study explains high platelets in ovarian cancer patients; survival reduced

16 Feb 2012
Study explains high platelets in ovarian cancer patients; survival reduced

Highly elevated platelet levels fuel tumour growth and reduce the survival of ovarian cancer patients, an international team of researchers led by scientists at The University of Texas MD Anderson Cancer center reports in the New England Journal of Medicine.

By pinpointing a powerful cause-and-effect relationship at the heart of a clinical observation that dates back more than 100 years, the team's findings reveal a new factor in cancer progression and new potential approaches for treatment.

"We've long known that ovarian cancer patients often have markedly increased platelet counts but we haven't known why this happens or understood its relevance, if any, to disease progression," said senior author Anil Sood, M.D., professor in MD Anderson's Departments of Gynaecologic Oncology and Reproductive Medicine and Cancer Biology.

"Our collaborative study not only identified a mechanism that explains platelet count elevation, but also connects this state, called thrombocytosis, to the severity of ovarian cancer," Sood said. "This suggests drugs that interfere with coagulation might be a useful addition to conventional therapies."

Drawing on clinical data from ovarian cancer patients and following up with mouse model experiments and a clinical trial, Sood and colleagues discovered:

Ovarian cancers produce the inflammatory cytokine interleukin-6 (IL-6); triggering creation of the platelet-production regulating hormone thrombopoietin (TPO) in the liver; causing platelet counts to soar to more than 450,000 per cubic millimeter in the blood, the threshold for thrombocytosis, and stimulating tumour growth and continuation of the cycle.

"Platelets may function as a fuel depot for tumours by providing them with growth factors," Sood said. They were found not only in the blood but also in the tumour's microenvironment, in the tumour bed, and in ascites, fluid build-up in the abdominal cavity common in ovarian cancer.

In a clinical trial conducted at the Barts Cancer Institute, Queen Mary, University of London, the team also found that treatment of 18 ovarian cancer patients in a phase I/II clinical trial with siltuximab, an antibody to IL-6, sharply reduced platelet counts over a three-week period.


Source: University of Texas M. D. Anderson Cancer Center