Bovine (cow) cartilage and shark cartilage have been investigated as treatments for cancer, psoriasis, arthritis, and a number of other medical conditions for more than 30 years.[1-13] Reviewed in [14-20] At least some of the interest in cartilage as a treatment for cancer arose from the mistaken belief that sharks, whose skeletons are made primarily of cartilage, are not affected by this disease. Reviewed in [16,21,22] Although reports of malignant tumors in sharks are rare, a variety of cancers have been detected in these animals. Reviewed in [21-24] Nonetheless, several substances that have antitumor activity have been identified in cartilage.[25-47] Reviewed in [2-4,7,15-20,46,48-50] More than half a dozen clinical studies of cartilage as a treatment for cancer have already been conducted,[2-4,7-9,50,51] Reviewed in [6,15-19] and additional clinical studies (MDA-ID-99303 and AETERNA-AE-MM-00-02) are now under way. Reviewed in [6,15,51]

The absence of blood vessels in cartilage led to the hypothesis that cartilage cells (also known as chondrocytes) produce one or more substances that inhibit blood vessel formation. Reviewed in [28-31,36,37,49] The formation of new blood vessels or angiogenesis is necessary for tumors to grow larger than a few millimeters in diameter (i.e., larger than approximately 100,000 to 1,000,000 cells) because tumors, like normal tissues, must obtain most of their oxygen and nutrients from blood. Reviewed in [34,35,42,52-55] A developing tumor, therefore, cannot continue to grow unless it establishes connections to the circulatory system of its host. It has been reported that tumors can initiate the process of angiogenesis when they contain as few as 100 cells.[54] Inhibition of angiogenesis at this early stage may, in some instances, lead to complete tumor regression.[54] The possibility that cartilage could be a source of one or more types of angiogenesis inhibitors for the treatment of cancer has prompted much research.

The major structural components of cartilage include several types of the protein collagen and several types of glycosaminoglycans, which are polysaccharides. Reviewed in [20,30,31,40,49,55,56] Chondroitin sulfate is the major glycosaminoglycan in cartilage. Reviewed in [40,55] Although there is no evidence that the collagens in cartilage, or their breakdown products, can inhibit angiogenesis, there is evidence that shark cartilage contains at least one angiogenesis inhibitor that has a glycosaminoglycan component (refer to the Laboratory/Animal/Preclinical Studies section of this summary for more information).[47] Other data indicate that most of the antiangiogenic activity in cartilage is not associated with the major structural components. Reviewed in [27,31,49]

Some glycosaminoglycans in cartilage reportedly have anti-inflammatory and immune-system –stimulating properties,[57,58] Reviewed in [1,2,14,16] and it has been suggested that either they or some of their breakdown products are toxic to tumor cells.[25] Reviewed in [2,3] Thus, the antitumor potential of cartilage may involve more than one mechanism of action.

Cartilage products are sold commercially in the United States as dietary supplements. More than 40 different brand names of shark cartilage alone are available to consumers. Reviewed in [18] In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because manufacturers of cartilage products are not required to show evidence of anticancer or other biologic effects, Reviewed in [18] it is unclear whether any of these products has therapeutic potential. In addition, individual products may vary considerably from lot to lot because standard manufacturing processes do not exist, and binding agents and fillers may be added during production. Reviewed in [18] The FDA has not approved the use of cartilage as a treatment for cancer or any other medical condition. The FDA is notifying consumers of a refund program for purchasers of Lane Labs-USA, Inc.'s, BeneFin, its shark cartilage product. Consumers are eligible for a partial refund of the purchase price and any shipping and handling costs if this product was purchased between September 22, 1999 and July 12, 2004.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. To date, IND status has been granted to at least four groups of investigators, one of which is the MDA-ID-99303 trial, to study cartilage as a treatment for cancer. [7,59] Reviewed in [19] Because the IND application process is confidential and because the existence of an IND can be disclosed only by the applicants, it is not known whether other applications have been made.

In animal studies, cartilage products have been administered in a variety of ways. In some studies, oral administration of either liquid or powdered forms has been used.[20,40,41,44,45,60] Reviewed in [15,48] In other studies, cartilage products have been given by injection (intravenous or intraperitoneal), applied topically, or placed in slow-release plastic pellets that were surgically implanted.[27,28,33,34,36,39,41,43,45] Reviewed in [29,47,49] Most of the latter studies investigated the effects of cartilage products on the development of blood vessels in the chorioallantoic membrane of chicken embryos, the cornea of rabbits, or the conjunctiva of mice.[27,28,33,36,39,41,43,45] Reviewed in [29,47,49]

In human studies (MDA-ID-99303, AETERNA-AE-MM-00-02, and NCCTG-971151), cartilage products have been administered topically or orally, or they have been given by enema or subcutaneous injection.[2-4,7-9] Reviewed in AETERNA-AE-RC-99-02,[6,15-17,19,61] For oral administration, liquid, powdered, and pill forms have been used as described in MDA-ID-99303, NCCTG-971151, and AETERNA-AE-MM-00-02.[2-4,7-9] Reviewed in [6,15-17,19] The dose and duration of cartilage treatment have varied in human studies, in part because different types of products have been tested.

In this summary, the brand name (i.e., registered or trademarked name) of the cartilage product(s) used in individual studies will be identified wherever possible.

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