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 ¹ and AETERNA-AE-MM-00-02 ²) 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 ³ 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 ⁴), 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 ⁵,[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.

References

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Glossary Terms

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels needed for tumors to grow. This is caused by the release of chemicals by the tumor.

A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of new blood vessels needed for tumors to grow.

Having to do with reducing inflammation.

Having to do with reducing the growth of new blood vessels.

A disease that causes inflammation and pain in the joints.

A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders.

A tube through which the blood circulates in the body. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

A tough, flexible tissue that lines joints and gives structure to the nose, ears, larynx, and other parts of the body.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Cartilage cell. Chondrocytes make the structural components of cartilage.

The major glycosaminoglycan (a type of sugar molecule) in cartilage.

The membrane in hens' eggs that helps chicken embryos get enough oxygen and calcium for development. The calcium comes from the egg shell.

The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial.

A fibrous protein found in cartilage and other connective tissue.

A membrane that lines the inner surface of the eyelid and also covers the front part of the eye. Conjunctivitis is inflammation of the conjunctiva.

The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside.

The length of a straight line that extends from one edge of a tumor or other object, through its center and to the opposite edge. It is usually used to measure the size of round or spherical shapes.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

The amount of medicine taken, or radiation given, at one time.

Early stage in the development of a plant or an animal. In vertebrate animals (have a backbone or spinal column), this stage lasts from shortly after fertilization until all major body parts appear. In particular, in humans, this stage lasts from about 2 weeks after fertilization until the end of the seventh or eighth week of pregnancy.

The injection of a liquid through the anus into the large bowel.

An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently.

A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye.

A tentative proposal made to explain certain observations or facts that requires further investigation to be verified.

The complex group of organs and cells that defends the body against infections and other diseases.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

IP. Within the peritoneal cavity (the area that contains the abdominal organs). Also called IP.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

A researcher in a clinical trial or clinical study.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

A measure of length in the metric system. A millimeter is one thousandth of a meter. There are 25 millimeters in an inch.

By or having to do with the mouth.

A large carbohydrate molecule. It contains many small sugar molecules that are joined chemically. Also called glycan.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A chronic disease of the skin marked by red patches covered with white scales.

A decrease in the size of a tumor or in the extent of cancer in the body.

The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage.

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Beneath the skin.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

Having to do with treating disease and helping healing take place.

On the surface of the body.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.