Antiangiogenesis

Human Heart Blood SystemFor a  tumor to grow and metastasize it must have a blood supply.  Angiogenesis is the process by which new blood vessels, called capillaries, develop and grow. Angiogenesis occurs naturally in reproduction, in the development of the embryo, and in the healing process of wounds. Angiogenesis also occurs in several unnatural, pathological conditions such as rheumatoid arthritis, diabetic retinopathy, and cancer.  In the case of cancer, a tumor will not grow larger than 0.5 mm unless it obtains an ever increasing blood supply through the angiogenic process.

Tumors require an extensive network of blood vessels to supply the nutrients for its excessive cell growth. Thus, the tumor calls on many of the body mechanisms to acquire those needed blood vessels. If the tumor can be denied this continuing supply of new blood vessels, tumor growth will be inhibited or halted. Treatment to block angiogenesis is properly termed antiangiogenesis (AA).  It must be emphasized that antiangiogenesis will most likely not “cure” cancer.  It will slow or halt growth, which in turn will allow more time and opportunity for other cancer treatments to become effective. Endothelial cells line blood vessels, The tumor produces angiogenic substances to initiate endothelial cell growth, which in turn initiates capillary growth. These substances may be growth  factors particularly VEGF- vascular endothelial growth factor, proteases,  oncogenes, signal transduction enzymes, cytokines, endogenous modulators, etc. Many natural and alternative medicines are proposed to have AA activity, which may explain in part, why they show anticancer activity. The mechanisms of activity remain to be elucidated. Some of the products claimed to have AA activity are: alpha lipoic acid, bindweed, butcher’s broom, curcumin, genistein, green tea, honeylocust fruit, quercetin, selenium, shark cartilage, and silimarin.

There are two general approaches to antiangiogenetic therapy. One is to block these growth factors; there are several such blocking agents, such as Avastin, being developed by various drug companies. They are in clinical trial and show promise, and also promise to be expensive if and when available. Further, as with many new drugs, adverse effects are being found, which may not outweigh their potential in cancer therapy. These drugs are currently for clinical trial only, and access requires participation in such trials.

A second approach is to deny a tumor the one component absolutely required for blood vessel growth - copper. Tumors hoard copper containing about three times the normal tissue levels of this mineral. Normal tissue function remains intact when the copper levels are only lowered but a tumor’s abnormal needs are  denied. Unlike the first approach , there is already a drug available. An agent with orphan drug status for the treatment of Wilson’s disease is available and works by decreasing body copper levels. Tetrathiomolybdate (TM) selectively chelates copper and has been safely used for many years in the treatment of Wilson’s disease. Initial studies indicate that it can decrease cancer cell growth. There are at least nine clinical trials of TM in progress, and these trials will attempt to prove activity in several cancer types. 

Tetrathiomolybdate treatment requires a month or more to reduce copper levels; then the patient must be maintained at this low copper level for several months. As with all cancer treatment, the sooner treatment starts the more likely there will be success. The treatment procedure is rigorous with regard to dosage timing, diet, and other restrictions. This is not a treatment to be individually undertaken. We cannot over stress the absolute need for patients using TM therapy to be in the care of a physician and be continually monitored for the duration of the treatment. Drug adjustments will likely be required over time to maintain the desired effect. As adjuvants to TM treatment, both vitamin C and zinc,if taken with meals, will decrease copper uptake. 

We feel that TM will become a major component of successful cancer therapy in both conventional and alternative  medicine. However, we also feel that TM’s potential will only be realized when TM is rationally combined  with other modalities, both while copper levels are being lowered, and later when the low copper level is being maintained. Time is never on the side of the cancer patient. If cancer growth can be slowed or halted, this offers more time as well as opportunity for other therapies to actually kill the cancer. We feel that immune therapy will be greatly improved when combined with antiangiogenesis. It is also likely that some alternative treatments will show sufficient activity under these conditions to demand they be recognized.