Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Sep 2008
ReviewAbl tyrosine kinase inhibitors for overriding Bcr-Abl/T315I: from the second to third generation.
Treatment of chronic myeloid leukemia (CML) has changed drastically with the emergence of the Abl tyrosine kinase inhibitor (TKI), imatinib mesylate. However, primary and secondary resistance have frequently been reported, particularly in patients with advanced-stage disease. Point mutations within the Abl kinase domain that interfere with imatinib binding are the most critical cause of imatinib resistance. ⋯ Despite promising clinical results from these novel Abl TKIs for most mutations, the frequently observed mutant T315I is not effectively targeted by any of these agents. Thus, identification of novel agents and the development of new strategies for the effective treatment of CML patients with the T315I mutation are important and challenging tasks. In this review, the current status of novel agents for CML treatment is overviewed as follows: pathogenesis and features of CML; imatinib and second-generation Abl TKIs; why Abl TKIs are not effective against T315I; and novel agents that may override the T315I mutation.
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Expert Rev Anticancer Ther · Sep 2008
ReviewAndrogen receptor: role and novel therapeutic prospects in prostate cancer.
Androgen receptor (AR) signaling is necessary for the development of prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer was described over 50 years ago and ADT remains the mainstay of systemic therapy. ⋯ CRPC cells upregulate enzymes used in androgen synthesis, thus providing an intracellular source of androgen despite systemic castration. Compounds in development, such as antiandrogens, lyase inhibitors, heat-shock protein-90 inhibitors, histone deacetylase inhibitors and others, will provide new tools to more effectively reduce ligand, inhibit AR and/or inhibit costimulatory pathways and result in improved clinical outcomes.