Clin Cancer Res
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The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. ⋯ Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.
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Platinum drugs are major chemotherapeutic agents that are used alone or in combination with other systemic agents and/or radiation therapy in the management of many human malignancies. All three platinum drugs approved by the Food and Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated intravenously. Satraplatin is the first orally administered platinum drug under active clinical investigation. ⋯ The most mature clinical data for satraplatin come from the recently completed phase III trial that investigated the efficacy of satraplatin and prednisone on hormone-refractory prostate cancer patients who had failed a course of other chemotherapy agents. Preliminary reports show that the combination is statistically superior to placebo and prednisone in multiple end points, including progression-free survival, prostate-specific antigen response, objective tumor response, pain response, and duration of pain response. The difference in overall survival, however, did not reach statistical significance.
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The epothilones are macrolide compounds that have been shown to stabilize microtubules. The epothilones are strong promoters of tubulin polymerization in vitro and have significant antitumor activity against human cancer cells that are taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have acquired tubulin mutations. Several epothilones have been evaluated in clinical trials in a variety of tumor types. ⋯ Food and Drug Administration for the treatment of patients with metastatic or locally advanced breast cancer. There have been sustained efforts to develop pharmacodynamic markers to monitor the pharmacologic effect of the epothilones on tumors and normal tissues. The development of predictive markers for epothilone chemotherapy is highly desired to provide more tailored therapy for patients with cancer.