The Reality of Targeted Therapies

Image: Courtesy of Mignon Fogarty LEARNING ABOUT RESISTANCE: Most cancers engage multiple growth factor, angiogenic, cell cycle, and apoptosis pathways. Frequently, redundant pathways exist, so that as drugs shut one pathway down another pathway takes over. This is one way that cancers become resistant to targeted agents. Early stage tumors tend to secrete a small number of pro-angiogenic factors, whereas late stage tumors secrete a larger number of pro-angiogenic factors. Targeted anti

Written byMignon Fogarty

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Targeted anticancer agents have had their ups and downs lately. While Gleevec, Herceptin, and Rituxan are proving useful in a broader array of patients with cancer than initially expected, other targeted agents have disappointed in pivotal clinical trials. In August, AstraZeneca's epidermal growth factor receptor (EGFR) inhibitor, Iressa, failed a Phase III trial in patients with non-small-cell lung cancer (NSCLC). Preclinical studies indicated that Iressa would act synergistically with chemotherapy, but the combination treatment showed no effect on survival benefit. Then, less than a month later, Avastin, Genentech's much-touted vascular endothelial growth factor (VEGF) inhibitor, joined the long list of failed angiogenesis inhibitors1 when it belly-flopped in its first Phase III trial, where it was combined with chemotherapy to treat metastatic breast cancer. And in mid-September, Theratope from Biomira failed to meet interim endpoints in a Phase III trial in patients with breast cancer. Theratope is intended to stimulate the ...

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