"To answer these questions, one has to divide cancers into two groups: solid tumors that require the development of a blood supply to metastasize and enlarge, and soft tumors that may have circulating cells, as in leukemias.
"Almost half the deaths from cancers result from lung and breast cancer, both of which are solid tumors. Gene therapy has found very little success in treating these types of cancers. If you are going to try to change the genetic makeup of the cancer cells by inserting genes, you must first get the genes to the cancer cells. Currently direct injection of genes into the cancer mass is being attempted, but it is unlikely that it will work because all the cells must be hit, which is very unlikely.
"Most cancers kill their victims by metastasis, wherein cancerous cells move from the primary site to other places in the body. It would be almost impossible to inject genes directly into all these sites. Furthermore, a cancer is not made up of only one type of rapidly, uncontrolled growing cell but has many different types of cells, some of which might not respond to the gene you wish to insert. Gene therapy within the next decade or so is not going to prove very effective in eliminating solid cancers such as lung, breast, prostate, colon and so on. There has been limited success with cancers where cells are circulating in the bloodstream or even in the bone marrow; these cancers are relatively few in number, although they do claim many lives every year. It is in these cases, I think, that gene therapy has the best chance of working.
"Are there other new therapies? Yes! At present, the majority are adjunct therapies to existing chemotherapy treatments. Most cancers must develop a blood supply to continue growth beyond a few millimeters in size. Nutrients and oxygen carried in the blood must be delivered to the cancer, and wastes must be removedQotherwise the cancer cells, like any other cells in a tissue, will die. Without a blood supply, cancer cells do not effectively metastasize to other organs and thereby kill the patient. Medical researchers are now testing many therapeutic agents intended to prevent blood supply to tumors. Some of these agents appear to halt cancer growth, which would then allow conventional chemotherapy treatments to work more effectively.
"Another approach being explored in my lab and in a couple of others involves identifying molecules that are found only on the surface of the blood vessels feeding the cancers (and not on the surface of blood vessels in normal tissues). Once these molecules are identified, they can be used as 'zip codes' to address various therapeutic agents only to the cancer or to send agents to block the blood supply to the cancer without killing the surrounding, normal cells. Furthermore, using the specific molecules on the surface of the cancer blood vessels to target therapeutic agents raises the possibility of using the same molecules to target agents to the cancer cells as well. It may even be possible to modify the cancer blood vessel cells to secrete factors that would inhibit cancer cell growth.
"I have great hopes for the targeting approach. My colleagues and I recently wrote a short review of the approach, published in the April 1996, issue of Nature Medicine.
Jim Mixson of the University of Maryland School of Medicine also provided a two-part answer to the question:
"Regarding the first part of the question, gene therapy is approaching clinical realization for the treatment of neoplastic and metabolic diseases. Although currently there are no FDA-approved gene therapy products, an effective gene therapy will probably gain FDA approval within the next three to five years. There are now more than 100 gene therapy clinical trials aimed toward cancer, genetic diseases (such as ADA deficiency, cystic fibrosis and hemophilia A), infectious diseases (including AIDS) and autoimmune diseases (such as rheumatoid arthritis). Because of the urgent needs of a large number of cancer patients, most of these gene therapy trials are directed against cancer.
"Gene therapy approaches fall into two main categories: (1) the transfer of a gene that stimulates the immune system and (2) the insertion of genes within the tumor that sensitizes the tumor to a relatively nontoxic 'prodrug.' Both these approaches show a great deal of promise."
The second part of Mixson's answer echoes the research described by Jacobson:
"Therapies that inhibit tumors' blood vessel development also seem to have considerable merit. Blood vessel development is technically known as angiogenesis, so the drugs that inhibit this process are called antiangiogenic. These antiangiogenic drugs include antibiotic derivatives, peptides (small protein fragments) and peptide derivatives. Many of the peptides being tested have been isolated from proteins that are secreted by tumors. Blood vessel development is critical for the growth of any solid tumor, such as breast, colon or lung cancer. Thus, any therapy that can inhibit the tumors' blood supply should be effective against multiple types of tumors. This area of research is receiving a good deal of attention, and there are already clinical trials in this field.