Research has shown that controlling production of new blood vessels can restrict tumor growth, often prolonging the life of the cancer patient.  Perhaps the most widely-used anti-angiogenic agent to emerge to date is a drug called bevacizumab (AvastinŽ, Genentech).  Bevacizumab was approved by the FDA for use in combination with intravenous 5-fluorouracil-based chemotherapy for first-line treatment of patients with metastatic colorectal cancer.  However, bevacizumab has also shown activity in many other solid tumor types such as breast, lung, and ovarian cancers.  As with most targeted-therapy drugs, bevacizumab does not necessarily benefit every patient and it is expensive.  Further, no test currently exists that shows reliably who will benefit from it.

 

The Weisenthal Cancer Group has developed an assay for microvascular viability (M.V.V.) to identify potential responders to bevacizumab, sorafenib, sunitinib, and other anti-angiogenic drugs and to assess previously unanticipated direct and potentiating anti-angiogenic effects of targeted therapy drugs such as erlotinib and gefitinib.  Click here for a link to an article in Journal of Internal Medicine reporting development of the assay.  Prior to development of the M.V.V. assay it was thought that the lack of an intact tumor micro-vasculature would prevent in vitro drug studies in disaggregated tissues.  However, it was discovered that endothelial cells are present in tumor microclusters and it appears that drug effect upon these cells can be assessed in the M.V.V. assay (see diagram below).  Confirmatory activities are ongoing.  A patent application has been submitted which covers a range of sample preparation, assay targeting, drug exposure, sample analysis, and scoring methods.  The M.V.V. assay is being offered as an adjunct to either a Weisenthal Cancer Group standard assay or an EGFRx™ tyrosine kinase assay.  (click here to see sample M.V.V. assay reports). 

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AngioRx™ Microvascular Viability / Angiogenesis Assay
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mvv diagram
M.V.V. Assay Principle
Living cells in culture, NOT exposed to anti-VEGF drug.  Undamaged membranes of microcapillary cells exclude vital dye.  No visible staining.
Leaky membranes of dead and dying cells admit vital dye, which then extrudes into adjacent spaces during alcohol-based counterstaining.  Note that anti-VEGF drug does not damage tumor cells in the mixed cell population.
Mixed population of cells in a microcluster.  CD31 staining confirms the presence of endothelial cells.