Our understanding of the biological processes which govern carcinogenesis is growing rapidly and provides the basis for identifying novel cellular targets for anticancer drug development. New approaches that are designed to exploit biological derangements unique to the cancer cell are being tested in clinical trials. Examples include:
• Matrix metalloproteinase inhibitors that are designed to inhibit invasion of cancer cells and prevent formation of metastases.
• Inhibitors of angiogenesis. Tumours require nutrition and produce angiogenic signals that lead to new vessel formation; the strategy is to prevent new blood vessel formation essential for tumour growth.
• Signal transduction inhibitors. An example is farnesyl transferase, an enzyme crucial for the activation of the oncogene, ras, which is frequently overexpressed in cancers. Inhibitors of this enzyme appear effectively to inhibit cancer cell growth.
• Designer molecular therapy. A tyrosine kinase inhibitor, imatinib, is specifically designed to block the dysregulated tyrosine kinase hyperactivity produced by the Philadelphia chromosome that is specific for chronic granulocytic leukaemia; clinical trials support its efficacy in this disease.
• Agents that promote apoptosis are being developed for clinical use.
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