title: Tyrosine kinase inhibitors in the treatment of prostate cancer: taking the next step in clinical development.
abstract: BACKGROUND
  Prostate cancer (PCa) is the most frequently diagnosed, non-cutaneous malignancy in Western countries. Until recently, few therapeutic options were available for patients with advanced PCa. Although these treatments may delay progression of disease, none are curative. Therefore, research continues to investigate other treatments for advanced PCa. Tyrosine kinase inhibitors (TKIs) have been extensively studied as a treatment for multiple malignancies and may represent an additional strategy. In addition to limiting cellular proliferation and metastasis, there is also growing interest in using these treatments to impact the bone microenvironment and reduce associated morbidity from PCa.
  
  
  METHODS
  Several TKIs have been evaluated in the preclinical setting in advanced PCa. Targets reviewed include the epidermal growth factor family, VEGF receptor, c-Src family kinases, platelet-derived growth factor and c-Met.
  
  
  CONCLUSIONS
  Despite strong biological rationale for the use of TKIs therapy for the treatment of PCa, Phase III clinical trials have produced disappointing results. As TKI strategies move forward, the failures of past trials need to be better understood. New approaches with these treatments will also have to take into account modern anti-androgens and a treatment landscape that now includes immunotherapy.
authors.affiliation: Clinical Fellow,National Cancer Institute, Medical Oncology Branch , 9000 Rockville Pike Bldg 10, Rm 12N226, Bethesda, MD 20892 , USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Ojemuyiwa
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Madan
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: EGFR; VEGF; c-Src family kinases; castrate-resistant metastatic prostate cancer; platelet-derived growth factor; prostate cancer; tyrosine kinase inhibitor