High platelets in ovarian cancer may be treatment target
Scientists have identified a mechanism that explains platelet count elevation in ovarian cancer, and have connected this state of thrombocytosis to disease severity. The new information suggests that drugs that interfere with coagulation could be a useful addition to conventional therapies.
Although it was previously known that women with ovarian cancer often have markedly increased platelet counts, the mechanism driving this occurrence and the effects of the platelets on tumor growth and angiogenesis were unclear. Now, investigators have found that thrombocytosis is significantly associated with advanced disease and shortened survival.
After analyzing data from 619 women with epithelial ovarian cancer, the researchers ascertained that 192 (31%) had thrombocytosis. However, less than 2% of this subgroup had an iron deficiency or a noncancerous inflammatory condition, which are the two most common causes of elevated platelet levels. The women with thrombocytosis survived for a median of 2.62 years, compared with 4.65 years for patients with normal platelet counts. Mouse models demonstrated elevated platelet counts in epithelial ovarian cancer, pancreatic cancer, and uterine cancer, but not in breast cancer.
The researchers learned that ovarian cancers produce the inflammatory cytokine interleukin-6 (IL-6). The liver responds by producing thrombopoietin (TPO), a hormone that regulates platelet production. Platelet counts then soar to more than 450,000 per cubic millimeter of blood—the threshold for thrombocytosis—fueling tumor growth and perpetuating the cycle.
Research involving mice as well as human subjects indicated that administering an antibody to IL-6 sharply reduced platelet counts (N Engl J Med. 2012;366:610-618).