RC: The brilliant concept of Judah Folkman's (I think he deserves a Nobel for Medicine) that cutting the fuel-line of cancer cells, i.e. by inhibiting its blood supply, is a viable alternative to cytoreductive therapies for cancer has taken firm root by now, although it took almost 30 years from the time it was first proposed (See "Tumor Angiogenesis:Therapeutic Implications. New Eng J Med 1971:285 pp 1182-1186). When I first embraced the idea and used this approach with relatively primitive agents (alpha-interferon, tetracyclines, shark's cartilage) in the late '90s, I was very hopeful but yet did not see dramatic results. Much hoopla has been supplanted by realism: while on one hand we know much more today than just a few years ago about angiogenesis and its control, we have also awakened to the reality that anti-angiogenesis alone (especially with single agents) usually does not do the job of stopping cancer growth. There are many "alternatives" in this arena: from off-label drugs such as cox-2 inhibitors to investigational agents such as the copper-chelator tetrathiomolybdate and many many supplements and herbs which have been found to have antiangiogenic effects in vitro.

Those interested in this area should read the saga of this concept's development as chronicled in the biography of the maverick scientist-physician Judah Folkman. For a beautiful introduction to angiogenesis and cancer, the online article by Steven Brem MD at the Mofitt in "Angiogenesis and Cancer Control: From Concept to Therapeutic Trial."

Many many agents (See growing and partial list below!) of all kinds have antiangiogenic activity although some of them are impractical or toxic to use (Squalamine, Suramin), others are weak (spironolactone), and still others are not yet clinically established. Some agents (eg shark's cartilage) stirred much hope but proved to be unremarkable at the end.

Angiogenesis may not be as powerful as we hoped but has proven clinial efficacy (as in the cases of the new drugs targeting EGFR Iressa and Avastin), but they are not as toxic as cytoreductive therapies and have broad applicability to both solid and hematologic tumors. Again, in concert with a central theme of this site, I firmly believe that a cocktail approach to angiogenesis (which involves many biological switches and pathways) and indeed a combined multi-tiered cocktail approach to cancer combining anti-angiogenesis and apoptosis and immunotherapy may be the ultimate goal.

Potentially useful antiangiogenic agents include:

2-methoxy-estradiol

biphosphonates

captopril

Chinese herbs (such as Thunder God Vine)

Cox-2 inhibitors (e.g. celebrex)

cromolyn sodium (Nasalcrom)

cyclosporin

curcumin

ECGC

heparins

interferons

metronomic chemotherapy

neomycin

omega-3 fatty acids

penicillamine

PSP

retinoids

spironolactone

squalamine

steroids

suramin

tetracyclines

tetrathiomolybdate

thalidomide

trientine (Syprine)

Vitamin E's