Blood Test Offers Specific Treatment for Ovarian Cancer

A new blood test has been developed allowing doctors to predict which ovarian cancer patients will respond to particular types of treatment.

Ovarian cancer is the fourth most common cause of female cancer-related death, accounting for thousands of lives each year and for several decades the standard of care has been surgery and platinum-based cytotoxic chemotherapy.

Scientists at the University of Manchester (UK) and their colleagues collected blood samples from patients enrolled in an international trial of bevacizumab. These patients received the standard chemotherapy treatment alone or chemotherapy plus the blood vessel-targeting drug. This included blood samples from 91 pretreatment training and 114 validation patients. Plasma concentrations of 15 angio-associated factors were determined using validated multiplex enzyme-linked immunosorbent assays (ELISA).

The ELISAs were performed using the SearchLight Plus charged couple device imaging system (Aushon BioSystems; Billerica, MA, USA). Angiogenesis-associated protein concentrations were assessed using two six-plex ELISAs of angiopoietin-2 (Ang2) , fibroblast growth factor (FGFb), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGFbb), vascular endothelial growth factors (VEGFA and VEGFC) and granulocyte colony–stimulating factor (GCSF), interleukin, IL8 (IL8), keratinocyte growth factor (KGF), placental growth factor (PlGF), VEGF receptors (VEGFR1, and VEGFR2), respectively, a duplex of Ang1 and Tunica internal endothelial cell kinase 2 (Tie2) and a single plex of VEGFD.

Among women with high Ang1 and low Tie2 plasma concentrations, there was a greater chance of tumor response after bevacizumab treatment compared with standard treatment. Specifically, the effective predictor of a beneficial effect of bevacizumab was the combination of a supra-median concentration of Ang1 and an infra-median concentration of Tie2. The biomarker combination provides predictive information, over and beyond, that provided by the two markers individually. The biologic implication of these finding is that the Ang1–Tie2 axis may play a pivotal role in mediating resistance to VEGF pathway inhibitors. The authors concluded that that ovarian cancer, which is an angiogenesis-dependent disease, might be categorized into VEGF or Ang inhibitor–sensitive disease. The question remains of whether treatment with one inhibitor leads to escape through the alternate mechanism.

Gordon C. Jayson, FRCP, PhD, a Professor of Medical Oncology and senior author of the study, said, “We are keen to identify predictive biomarkers, measures that can indicate how well a patient will respond to treatment, so we can better target these drugs to patients most likely to benefit. We investigated levels of a range of proteins in patients' pretreatment blood samples to see if any were associated with improved survival.” The study was published on September 1, 2014, in the journal Clinical Cancer Research.

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