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Old 09-11-2008, 05:09 PM
gdpawel gdpawel is offline
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Default Antivascular activity of lapatinib and bevacizumab in primary microcluster cultures

Antivascular activity of lapatinib (Tykerb) and bevacizumab (Avastin) in primary microcluster cultures of breast cancer and other human neoplasms

Sub-category: New Systemic Agents - New drugs and targets (includes anti-angiogenics) - Other

Category: Treatment

Meeting: 2008 Breast Cancer Symposium

Abstract No: 166

Author(s): L. Weisenthal, D. J. Lee, N. Patel

Abstract:

Background:

The following tyrosine kinase inhibitors (TKI) have been shown to have antivascular (AV) activity: sunitinib (Su), sorafenib (So), gefitinib (G), erlotinib (E), and imatinib (I). To date, AV activity has not been reported for lapatinib (LAP).

Methods:

We studied the ability of TKI to induce tumor cell death (TCD) and also endothelial cell death (ECD) in primary human tumor cultures, using a novel functional profiling assay system, which detects TCD vs ECD in floating cell microclusters derived with > 90% success rate from fresh human tumor biopsies (Weisenthal, 2007 ASCO GI Symposium Abst 439; [url]http://tinyurl.com/ywfnsy;[/url] Weisenthal, et al. J Intern Med, In Press).

Results:

LAP (15

Last edited by gdpawel : 09-11-2008 at 05:49 PM.
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Old 09-11-2008, 07:43 PM
gdpawel gdpawel is offline
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Default Primary Microcluster Culture Studies

Direct anti-tumor and anti-vascular effects were studied of Tykerb, Nexavar and Avastin in fresh biopsy specimens of breast cancer and presented at the American Society of Clinical Oncology Breast Cancer Symposium on September 5, 2008.

While the other clinically-available 'nib' drugs have been shown to have anti-vascular activity, anti-vascular activity of Tykerb has not been previously reported.

Angiogenesis studies are limited by the clinical relevance of laboratory model systems. They don't do "real world" studies under "real world" conditions. Patient outcomes need to be reported in real-time, so patients and cancer physicians can learn immediately if and how patients are benefiting from new drug therapies.

Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood can identify the activity of both single drugs and combinations of drugs at the level of individual patients with individual cancers. It works by measuring drug effects (real-time) upon endothelial cells which make up blood vessels.

Drugs like Avastin had striking anti-microvascular effects but minimal anti-tumor effects. Tarceva and Gleevec had mixed antitumor and anti-microvascular effects. Anti-microvascular effects of Tarceva and Iressa were equal to those of Sutent and Nexavar. Anti-microvascular additivity was observed between Avastin and other drugs on an individual basis.

Conclusions of the study had shown that Tykerb has antivascular activity superior to that of Nexavar. Avastin + Tykerb may be the first clinically-exploitable antivascular drug combination. High dose, intermittent 'bolus' schedules of Tykerb to coincide with Avastin administration may be clinically advantageous, even in HER2-negative tumors.

The system utilized for the study was a functional profiling assay, which may be used to individualize antivascular therapy. It can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of neoplastic and non-neoplastic conditions, for drug development, and individualized cancer treatment.

The cell-based assay can accurately sort drugs into categories of above average probability of providing clinical benefit on one hand and below average probability of providing clinical benefit on the other hand, based both on tumor response and patient survival.

[url]http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2008.01955.x/full

Last edited by gdpawel : 11-10-2012 at 01:50 PM. Reason: corrected url address
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