The CancerWeb Report, What's New In Cancer: December, 1996
Cancer in General

• A clue to a method to attack tumors by blocking their blood supply? - We have discussed in previous issues of CancerWeb Report, as well as in this month's issue under Breast Cancer - More on blood vessel numbers as an indicator of response to treatment, how it is absolutely necessary for a tumor to develop a blood supply if it is to survive and grow. It does this by making and secreting angiogenesis factors, substances that stimulate the outgrowth of new blood vessels from existing ones. If this process could be interrupted, the tumor would be unable to survive, or at least would remain tiny and pose no threat to life. The problem is that growth of new blood vessels is also required for normal processes such as repair of wounds, or increased blood supply to muscular tissue such as that of the heart in response to increased demands in an exercise program. If there were a way to distinguish malignant from benign blood vessel growth a selective approach might be possible. An article in the November, 1996 issue of Clinical Cancer Research by researchers at the University of California, Irvine, may offer hope of just such selectivity. They looked at the epithelial cells of the blood vessels and connective tissue associated with tumors in patients with gynecological cancers. All of 16 cases of uterine endometrial cancer and 12 of 15 cases of ovarian cancer stained positive for a protein called eosinophil peroxidase or EPO. This protein is normally present in granules within a special type of white blood cells called eosinophils, and is released when the cells secrete their granules. In these studies it appears that the EPO released by eosinophils is selectively taken up by the tumor blood vessel cells. The researchers were unable to find the protein in normal uterine tissue or ovaries, in normal tissue from the cancer patients removed from areas close to the tumors, or in any normal organs from 5 non-cancer patients on autopsy. EPO may not only be a new tumor marker, of which there are many others, but more importantly it may serve as a target for radiolabeled EPO antibodies that could deliver localized radiotherapy to the tumor. (Samoszuk, Clin Cancer Res 2:1867, 1996)

  Editor's Comment: - The prognostic value of microvessel counts has already been demonstrated, but the greater value resides in potential therapeutic use. This is a very promising approach to greater selectivity for tumor therapy. These Californian researchers have already demonstrated the feasibility of the approach in animals, as well as the specific localization of the antibody in patients with lymphomas. What is not yet known is how general this localization of EPO is for a range of tumor types, and whether there might be repercussions if any eosinophil destruction occurred.

  ---

• An effective way to give 5-fluorouracil by mouth? - 5-Fluorouracil (5-FU) is one of the oldest but most widely-used chemotherapy drugs. Unfortunately, because of the widely varying extent of its metabolism in the digestive tract and body tissues, which gives unpredictable levels of drug (variable bioavailability), it does not give consistent therapeutic results when given by mouth. Repeated injections or IV infusions are therefore necessary. A report by researchers at the Johns Hopkins Oncology Center in Baltimore, published in the December, 1996 issue of the Journal of Clinical Oncology, pointed a way to overcome this variability. In a small study, they administered a chemical, code named 776C85, which inhibits the metabolism of 5-FU, before and during treatment with 5-FU; both were given by mouth. Use of the chemical made the blood levels of 5-FU from oral drug more predictable and effective (100% bioavailable), and the researchers also found that there were fewer of those side-effects such as diarrhea and mucositis which do not involve the bone marrow. Further studies are underway. (Baker, J Clin Oncol 14:3085, 1996)