The CancerWeb Report, What's New In Cancer: July, 1996
Potential New Approaches to Therapy

• A new target for chemotherapy of breast cancer? - Most of the current chemotherapy drugs target one or two particular molecules or cell processes such as DNA synthesis or topoisomerase. There clearly is need to develop drugs that act at other potential targets in the cell, if we are to keep ahead of drug resistance and develop more effective combinations of agents. An article from the Johns Hopkins Medical School, appearing in the June 15, 1996 issue of Cancer Research, describes one such unexploited target, fat synthesis. Previously, these scientists among a number of others had shown that the synthesis of fatty acids in a range of types of cancer cells differed from that in normal cells in two major ways. Fatty acid synthesis is increased in the tumor, and tumors show a preference for using their own endogenous fatty acids in contrast to normal cells which preferentially use dietary fatty acids. In the present work, the researchers took human breast cancer cells and exposed them to cerulinin, an inhibitor of fatty acid biosynthesis. After a six-hour treatment, fatty acid synthesis was inhibited and the cells lost their ability to multiply. This was followed by breakage of their DNA and changes in the cells of the type associated with programmed cell death or apoptosis. (Pizer, Cancer Res 56:2745, 1996)

  Editor's Comment: - This work is at an early stage, but it shows great promise. We have an unexploited target for therapy, and an indication that the inhibitor works by turning on a natural pathway for tumor cells to commit suicide.

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• A new approach to cancer vaccine development? - Cancer vaccines remain elusive targets for research, in large measure because of the lack of antigen targets that are clearly tumor-specific, and the further difficulty in targeting them to produce an effective antitumor response. Human mucin MUC1 is very abundant in a number of cancers that are of epithelial origin, but only appears on the apexes of cells that produce secretions in normal tissues. Mucin has been explored by a number of researchers as a target for a vaccine, with some encouraging but not always consistent outcome in rodents. A new approach is described by a group of scientists at the Memorial Sloan-Kettering Cancer Center in New York, in the July 15, 1996 issue of Cancer Research. They took synthetic MUC1 peptide chains of different lengths, and attached them to a protein carrier, a hemocyanin derived from the keyhole limpet (KLH), and found that when used in combination with the immune adjuvant (stimulant) QS21, they could immunize mice against tumors that expressed MUC1. This immune reaction was due to antibody formation not stimulation of the T-cell system normally considered to be the major immune defense against tumors. The researchers propose using a 30-unit peptide joined to KLH by a specific chemical linkage (m-maleimidobenzoyl-N- hydroxysuccinimide ester), together with QS21, in clinical trials. (Zhang, Cancer Res 56:3315, 1996)

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• A potential new approach to protecting normal tissues from chemotherapy? - The major limitation to cancer chemotherapy is the limited difference between normal and tumor cells which does not permit the greater selectivity of action obtained with antibiotics. While the search for more tumor selectivity continues actively, the other approach, of increasing the resistance of normal tissue to the effects of the drugs, also is receiving attention. One new possibility is to take advantage of the growth regulating pathways that fully control normal tissues but are disordered in tumor cells. A report from Myriad Genetics, a company in Salt Lake City, Utah, published in the July 15, 1996 issue of Cancer Research, suggests s possible new approach. The researchers constructed a model tumor cell system by genetically engineering the introduction of the p16 gene into melanoma cells that lacked it. This growth-controlling gene, was modified so that it could be turned on by the chemical isopropyl- 1-thio-beta-D-galactopyranoside (IPTG), and would then stop the cells from entering the division cycle, a so called G0-G1 block. The cells could stay arrested without division for 7 days without losing their ability to divide later, and while in this state were 10-100 times more resistant to several chemotherapy drugs. Normal cells express p16 as part of their normal growth control mechanism, but it is not yet known how this gene can be turned so as to arrest normal cell division. While the strategy is still only a remote promise, it is worth exploring. (Stone, Cancer Res 56:3199, 1996)