Mammograms- New Govt Guidelines - Can't Believe!

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   dmwolf

Avastin as a single agent is relatively ineffective in virtually all tumor types other than Renal because it is known to be driven by the vascular endothelial growth factor (VEGF) pathway. Beyond that, it appears largely to better deliver the effects of other classes of drugs.

Avastin may have the potential to improve the efficacy of standard combination chemotherapy. The combination of Avastin with other conventional standard therapy may be promising, particularly with regard to safety and efficacy.

Tumor growth is dependent on angiogenesis. Angiogenesis is dependent on VEGF. Anti-angiogenesis drugs like Avastin work by blocking the activity of VEGF to prevent the growth of new capillaries into the tumor and thereby sustain tumor growth.

Avastin directly binds to VEGF to directly inhibit angiogenesis, by choking off the blood vessels that provide a tumor with oxygen and nutrients. Tumors which secrete relatively low levels of VEGF, might be more susceptible to an agent like Avastin which works by blocking VEGF (its effects upon endothelial cells which make up blood vessels).

In cell culture analysis, which actually assesses the direct or indirect effect of a drug upon the cell, whether it is a tumor cell or an endothelial cell, VEGF happens to be the molecule which has been implicated in the process of Avastin on endothelial cells. Drugs like Avastin have striking anti-microvascular effects but minimal anti-tumor effects. That is the reason giving Avastin with combination anti-tumor agents.

If it were the only protein involved, then one would expect that VEGF expression would correlate with Avastin activity 100% of the time, but it was studied that it actually does so only about 20% of the time, and it may not be the only protein involved. There are other clinically-available anti-angiogenesis drugs that have been shown to have anti-vascular activity.

Whether VEGF acts alone (unlikely) or in combination with other proteins and other mechanical factors, it would be more beneficial to assess the net effect of all those factors.

Physicians may have to combine several targeted treatments to try an achieve cures or durable reponses for more complicated tumors like those that occur in the breast, colon and lung. The trick is figuring out which patients will respond, and the challenge is to figure out which patients to give these drugs to.

In cancer medicine, it's not a case of throwing targeted drugs at the problem. It's knowing "what" targeted drugs and "how" to use them in "individual" patients (not average populations).

Conclusions of a recent study had shown that 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 (J Intern Med 264:275-287, September 2008).

The system utilized for the study was a functional profiling assay, which can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of solid-tumor cancer conditions.