title: Drug development in prostate cancer.
abstract: Despite strategies aimed at early detection and treatment, prostate cancer remains a leading cause of morbidity and mortality among males. Current therapies have limited impact on the natural history of metastatic hormone-refractory prostate cancer (HRPC). With an improved understanding of tumor biology, including apoptosis, differentiation, cell cycling and signaling, and angiogenesis, many potential new targets for therapy have been unveiled. Modulation of these processes may result in cytotoxic or cytostatic effects. The evaluation of therapies based on manipulation of these targets may not be adequately addressed by current study designs and traditional parameters of efficacy. Examples of agents currently in clinical trials that illustrate some of the challenges presented to clinical investigators include monoterpenes such as perillyl alcohol (POH), vitamin D analogs, flavones such as flavopiridol, and angiogenesis inhibitors. Agents such as these are aimed at unique cellular targets and will require novel approaches to determine their clinical utility. Unfortunately, in the United States, only a small proportion of cancer patients, including prostate cancer patients, are enrolled in clinical trials. We must do better to efficiently assess promising new treatment approaches and improve outcome for our patients.
authors.affiliation: Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Ripple
authors.forename: G
authors.initials: G
authors.lastname: Wilding
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002986:Clinical Trials as Topic; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D019008:Drug Resistance, Neoplasm; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D039821:Monoterpenes; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010880:Piperidines / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D013729:Terpenes / Q000627:therapeutic use; D014807:Vitamin D / Q000031:analogs & derivatives
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D005419:Flavonoids; D039821:Monoterpenes; D010880:Piperidines; D013729:Terpenes; D014807:Vitamin D; C032208:perillyl alcohol; C077990:alvocidib; D018844:Cyclin-Dependent Kinases