Published online 21 November 2010 | Nature | doi:10.1038/news.2010.623 http://www.nature.com/news/2010/101121/ ... 0.623.html
About the most key statement in the article (when it comes to treatment) is, "most people agree that a single pathway is not going to do it." When you get rid of VEGF with Avastin, the body cranks out other types of blood vessel growth/survival factors.
The problem with Avastin is the same thing that was a problem with AZT for HIV/AIDS. Early results, then rapid resistance. Solution was combination therapy to attack different targets. With cancer, it's going to take combination antivascular therapy to make a difference.
Tumor vasculature needs VEGF to survive. Avastin removes VEGF, killing blood vessels. But other proangiogenic factors can substitute: FGF, PDGF, ephrin A1, angioprotein 1, IL-8 etc. We need to attack these other targets, as well.
If you can achieve this, then you may not even need the other drugs, which don't get into the tumor so well. But angiogenic attack provides true selective toxicity, something which is sorely lacking with all of the other treatments.
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.
As the article mentions "vascular mimicry," something I've written about on the board previously, 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 angiogenesis, co-option of existing blood vessels and vasculogenic mimicry. All must be inhibited to consistently starve tumors of oxygen.
While vasculogenic mimicry - some types of cancers form channels that carry blood, but are not actual blood vessels - with co-option, instead of growing new blood vessels, tumor cells can just grow along existing blood vessels. This process cannot be stopped with drugs that inhibit new blood vessel formation.
The consistent and specific cure or control of cancer will require developing and using a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness.
A sufficient number of independent methods of cell killing must be employed so that it is too improbable for a cancer cell to evolve that can escape death or inactivation. It must examine every cell in the body and must do so for a prolonged period of time.
Given the current state of the art, cell-based in vitro drug sensitivity testing (with functional profiling) could be of significant clinical value. One aspect of a functional profiling assay is that microvascular viability can measure dead microvascular cells in tissue, fluid and peripheral blood specimens to identify potential responders to anti-angiogenic drugs (Avastin, Nexavar, Sutent) and to assess direct and potentiating anti-angiogenic effects of tyrosine kinase targeted therapy drugs (Tarceva, Iressa).