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Old 06-06-2011, 11:55 AM   #2
gdpawel
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Biomarkers of Antiangiogenic Therapy

There are a number of new classes of drugs that target VEGF, at the protein level (Avastin), at the tyrosine kinase level (Nexavar, Sutent) and at the intracellular metabolic pathway mTOR (Afinitor, Torisel).

However, responses to any individual mechanism occurs in the miniority of patients. It is unclear why some patients repond to these interventions while others fail. In cell function analysis, it has found unexpectedly good response to conventional cytotoxic drugs following a failure to respond to these targeted agents.

This reinforces the need for cancer therapies to be individualized. It remines us that it is the good outcome of the patient not the therapy applied that constitute successful therapy.

Angiogenic attack provides true selective toxicity, something which is sorely lacking with all of our other treatments. The solution is to investigate the VEGF targeting agents in each individual patient's tissue culture, alone and in combination with other drugs, to gauge the likelihood that vascular targeting will favorably influence each patient's outcome.

The AngioRx microvascular viability assay is a laboratory test which identifies anti-angiogenic drug activity in live tumor microclusters. The test is capable of discriminating anti-tumor effect from anti-angiogenic effect in the same mixed-cell population.

It is the only known technology which discriminates the effects of different types of anti-angiogenic drugs within the same class of drugs and within different classes of drugs, and is capable of identifying synergistic effects among different angiogenic and non-angiogenic drugs in specific drug combinations.

Bibliography relevant to AngioRx Microvascular Viability Assay

1. Weisenthal, L. M. Patel,N., Rueff-Weisenthal, C. (2008). "Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood." J Intern Med 264: 275-287, 2008. doi: 10.1111/j.1365-2796.2008.01955.x

2. Weisenthal, L., Lee,DJ, and Patel,N. (2008). Antivascular activity of lapatinib and bevacizumab in primary microcluster cultures of breast cancer and other human neoplasms. ASCO 2008 Breast Cancer Symposium. Washington, D.C.: Abstract # 166.

3. Weisenthal, L. M. (2010). Antitumor and anti-microvascular effects of sorafenib in fresh human tumor culture in comparison with other putative tyrosine kinase inhibitors. J Clin Oncol 28, 2010 (suppl; abstr e13617)

4. Weisenthal, L., H. Liu, Rueff-Weisenthal, C. (2010). "Death of human tumor endothelial cells in vitro through a probable calcium-associated mechanism induced by bevacizumab and detected via a novel method." Nature Precedings 28 May 2010.

5. Eur J Clin Invest, Volume 37 (suppl. 1):60, 2007

6. Nagourney, R.A. Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)

7. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117
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