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Overview of Novel Anticancer Drug Targets

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There has been an explosion in the number of potential molecular targets that can be explored for selective cancer treatment. The stage is now set to translate years of productive cancer research into more patient-friendly anticancer therapeutics. At present, the challenge is how to identify bonafide and viable targets and efficiently exploit these for the development of selective nontoxic cancer therapies, to overcome the major drawbacks of onventional cytotoxic cancer chemotherapy. To this end, it is gratifying that the selective inhibition of some of these novel targets, especially those in mitogenic signal transduction pathways like HER-2 and bcr-abl tyrosine kinases, has resulted in successful treatments of cancer patients. HER-2 is targeted by the antibody traszumamab (Herceptin�), approved for the treatment of metastatic breast cancer (1 ), while bcr-abl tyrosine kinase is targeted by the small molecule drug STI571 (Imatinib, Gleevec), for the treatment of chronic myelogenous leukemia (CML) (2 ). Other promising therapies targeted to other signal transduction targets are in the pipeline, the most advanced probably being small molecules targeted to the epidermal growth factor receptor (EGFR) tyrosine kinase (3 ). This chapter will provide a broad overview of a wide range of emerging molecular targets, highlighting some of the strategies used to exploit them for molecularly-targeted cancer therapy, such as small molecules, antibodies, and antisense oligonucleotides.
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