title: Biomarkers to predict response to sunitinib therapy and prognosis in metastatic renal cell cancer.
abstract: Sunitinib is an orally-administered, multitargeted tyrosine kinase inhibitor. The main targets are vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-α, and PDGFR-β. Among therapeutic targeting agents, it is the best available in the USA for patients with metastatic renal cell cancer (RCC). Well-constructed clinical trials have led to the worldwide approval of various agents for RCC. However, in clinical practice, it remains difficult to determine the best treatment strategy with these agents. Therefore, the identification of biomarkers to predict response and side-effects and to select optimal dosages is urgently needed. Potential mechanisms of action and resistance need to be understood in order to make accurate predictions. This article briefly reviews candidate biomarkers of sunitinib therapy in terms of clinical variables, genetic factors, and circulating proteins and endothelial cells. Although further validation and implementation is necessary, if validated, biomarkers will help measure the therapeutic response in individual patients and establish treatment strategies for metastatic RCC.
authors.affiliation: Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan. takeshi.yuasa@jfcr.or.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Junji
authors.initials: J
authors.lastname: Yonese
authors.forename: Iwao
authors.initials: I
authors.lastname: Fukui
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D001711:Biotransformation / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002986:Clinical Trials as Topic; D016903:Drug Monitoring / Q000379:methods*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000097:blood*; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000097:blood*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011758:Pyrroles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000097:blood*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D007211:Indoles; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C098069:PIGF protein, human; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D017978:Receptors, Growth Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib