AVASTIN Treatment for O.C

avastin
My mom is on Avastin, methotrexate, and cytoxan for stage 4 primary peritoneal/ovarian cancer(she is 64 yrs old). Her disease is stable except for a recent spread to the breast. She has been on Taxotere/Carbo and Doxil previous to this combination of meds. I have read that Avastin can help to stabilize the disease. So far, my mom has tolerated these meds well.
I wish you the best.
Eileen

Avastin in Ovarian Cancer
Tumor growth is dependent on angiogenesis. Angiogenesis is dependent on vascular endothelial growth factor (VEGF). Avastin directly binds to VEGF to directly inhibit angiogenesis. Within 24 hours of VEGF inhibition, endothelial cells have been shown (AngioRx Assay) to shrivel, retract, fragment and die by apoptosis. This is what is measured with the assay, which simultaneously measures direct antitumor activity and antivascular activity, death of existing endothelial (and associated) cells.

If the anti-angiogenesis drugs (Avastin) work the way they are supposed to work they block the activity of VEGF, to prevent the growth of new capillaries into the tumor and thereby sustain tumor growth. Perhaps Avastin "sensitive" tumors secrete relatively low levels of VEGF. Tumors which secrete relatively low levels of VEGF might be more susceptible to an agent which works by blocking VEGF.

The rationale underlying the use of anti-angiogenesis drugs (Avastin) against ovarian cancer is that (1) VEGF pathways are strongly associated with the development of malignant ascites, malignant pleural effusions and carcinomatosis, and (2) both VEGF receptors and VEGF ligands can be over-expressed in ovarian cancer.

According to clinical oncologists involved with cell culture assay testing, Avastin appears to better deliver the effects of other classes of drugs. In other words, Avastin facilitates vascular access of cytotoxics to tumors. Just as the GOG0218 and ICON7 trial results have shown.

However, single-agent Avastin has not been showing up being very productive in cell function analysis. What may limit the effectiveness of Avastin is that there are multiple ways by which tumors can evolve that are independent of VEGF and independent of angiogenesis. Tumors can acquire a blood supply by three different mechanisms: angiogenesis; co-option of existing blood vessels; and vasculogenic mimicry. All must be inhibited to consistently starve tumors of oxygen.

Instead of growing new blood vessels, tumor cells can just grow along existing blood vessels. This process, called co-option, cannot be stopped with drugs that inhibit new blood vessel formation. Some types of cancers form channels that carry blood, but are not actual blood vessels. Drugs that target new blood vessel formation also cannot stop this process, called vasculogeneic mimicry. The realization is that starving tumors by shutting off their blood flow requires that all three mechanisms be addressed.

Also, there are other proangiogenic factors that can affect whether Avastin works or not, FGF, PDGF, ephrin A1, angioprotein 1, IL8, etc. You need to attack these other targets as well. That is why we need combination anti-angioRX. If you can achieve this, then you don't really need the other drugs, which don't get into the tumor so well. Angiogenic attack provides true selective toxicity, something which is sorely lacking with all of the other treatments.

It could be vastly more important to measure the net effect of all processes (systems) instead of just individual molecular targets (like VEGF). The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not just one or a few targets or pathways.

There are many pathways to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indiviudal trees.

Literature Citation:
Eur J Clin Invest 37 (suppl. 1):60, 2007
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117
"Cure: Scientific, Social, and Organizational Requirements for the Specific Cure of Cancer" A. Glazier, et al. 2005