title: Resistance to sunitinib in renal cell carcinoma: From molecular mechanisms to predictive markers and future perspectives.
abstract: The introduction of agents that inhibit tumor angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling has made a significant impact on the survival of patients with metastasized renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor of the VEGF receptor, has become the mainstay of treatment for these patients. Although treatment with sunitinib substantially improved patient outcome, the initial success is overshadowed by the occurrence of resistance. The mechanisms of resistance are poorly understood. Insight into the molecular mechanisms of resistance will help to better understand the biology of RCC and can ultimately aid the development of more effective therapies for patients with this infaust disease. In this review we comprehensively discuss molecular mechanisms of resistance to sunitinib and the involved biological processes, summarize potential biomarkers that predict response and resistance to treatment with sunitinib, and elaborate on future perspectives in the treatment of metastasized RCC.
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: sophie.joosten@mumc.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Joosten
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: l.hamming@student.maastrichtuniversity.nl.
authors.forename: L
authors.initials: L
authors.lastname: Hamming
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: p.soetekouw@mumc.nl.
authors.forename: P M
authors.initials: PM
authors.lastname: Soetekouw
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: mjb.essers.aarts@mumc.nl.
authors.forename: M J
authors.initials: MJ
authors.lastname: Aarts
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands; Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany. Electronic address: jurgen.veeck@mumc.nl.
authors.forename: J
authors.initials: J
authors.lastname: Veeck
authors.affiliation: Dept. of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: manon.van.engeland@mumc.nl.
authors.forename: M
authors.initials: M
authors.lastname: van Engeland
authors.affiliation: Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: vcg.tjan.heijnen@mumc.nl.
authors.forename: V C
authors.initials: VC
authors.lastname: Tjan-Heijnen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D015398:Signal Transduction / Q000235:genetics; D000077210:Sunitinib; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Biological tumor markers; Drug resistance; Kidney cancer; Renal cell carcinoma; Sunitinib; Targeted therapy