Antiangiogenic therapy for breast cancer

Hopeful · 05-25-2011, 06:08 AM

http://breast-cancer-research.com/content/12/5/209

Hopeful

gdpawel · 06-06-2011, 11:55 AM

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

gdpawel · 07-28-2011, 07:15 PM

Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood.

2008 Sep;264(3):275-87.
Weisenthal LM, Patel N, Rueff-Weisenthal C.
Weisenthal Cancer Group, Huntington Beach, CA 92647, USA. mail@weisenthal.org

BACKGROUND:

Angiogenesis studies are limited by the clinical relevance of laboratory model systems. We developed a new method for measuring dead microvascular (MV) cells in clinical tissue, fluid and blood specimens, and applied this system to make several potentially novel observations relating to cancer pharmacology.

METHODS:

Dead MV cells tend to have a hyperchromatic, refractile quality, further enhanced during the process of staining with Fast Green and counterstaining with either haematoxylin-eosin or Wright-Giemsa. We used this system to quantify the relative degree of direct antitumour versus anti-MV effects of Cisplatin, erlotinib (Tarceva), imatinib (Gleevec), sorafenib (Nexavar), sunitinib (Sutent), gefitinib (Iressa) and bevacizumab (Avastin).

RESULTS:

Bevacizumab (Avastin) had striking anti-MV effects and minimal antitumour effects; Cisplatin had striking antitumour effects and minimal anti-MV effects. The 'nib' drugs had mixed antitumour and anti-MV effects. Anti-MV effects of erlotinib (Tarceva) and gefitinib (Iressa) were equal to those of sunitinib (Sutent) and sorafenib (Nexavar). There was no detectable VEGF in culture medium without cells; tumour cells secreted copious VEGF, reduced to undetectable levels by bevacizumab (Avastin), greatly reduced by cytotoxic levels of cisplatin + anguidine, and variably reduced by DMSO and/or ethanol. We observed anti-MV additivity between bevacizumab (Avastin) and other drugs on an individual patient basis. Peripheral blood specimens had numerous MV cells which were strikingly visualized for quantification with public domain image analysis software using bevacizumab (Avastin) essentially as an imaging reagent.

CONCLUSIONS:

This system could be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating MV cells in a variety of neoplastic and non-neoplastic conditions, and for drug development and individualized cancer treatment.

http://onlinelibrary.wiley.com/doi/1...8.01955.x/full

Biomarkers of Antiangiogenic Therapy

http://cancerfocus.org/forum/showthread.php?t=3372

Rich66 · 08-03-2011, 10:08 PM

Why It Makes Sense To Keep Avastin Available For Women With Metastatic Breast Cancer

http://www.huffingtonpost.com/elaine..._b_916545.html