title: The evolving role of monoclonal antibodies in the treatment of patients with advanced renal cell carcinoma: a systematic review.
abstract: BACKGROUND
  While the majority of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors currently used for the therapy of metastatic renal cell carcinoma (mRCC) are small molecule agents inhibiting multiple targets, monoclonal antibodies are inhibitors of specific targets, which may decrease off-target effects while preserving on-target activity. A few monoclonal antibodies have already been approved for mRCC (bevacizumab, nivolumab), while many others may play an important role in the therapeutic scenario of mRCC.
  
  
  METHODS
  This review describes emerging monoclonal antibodies for treating RCC. Currently, bevacizumab, a VEGF monoclonal antibody, is approved in combination with interferon for the therapy of metastatic RCC, while nivolumab, a Programmed Death (PD)-1 inhibitor, is approved following prior VEGF inhibitor treatment. Other PD-1 and PD-ligand (L)-1 inhibitors are undergoing clinical development.
  
  
  CONCLUSIONS
  Combinations of inhibitors of the PD1/PD-L1 axis with VEGF inhibitors or cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors have shown promising efficacy in mRCC. The development of biomarkers predictive for benefit and rational tolerable combinations are both important pillars of research to improve outcomes in RCC.
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Pagliuca
authors.affiliation: b Department of Urology , European Institute of Oncology (IEO) , Milan , Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferro
authors.affiliation: c Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit , University of Bari , Bari , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lucarelli
authors.affiliation: d Division of Medical Oncology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori 'Fondazione G. Pascale' - IRCCS , Naples , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossetti
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bosso
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Puglia
authors.affiliation: e Dipartimento di Medicina Molecolare e Biotecnologie Mediche , University Federico II of Naples , Naples , Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Pignataro
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ascione
authors.affiliation: b Department of Urology , European Institute of Oncology (IEO) , Milan , Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: De Cobelli
authors.affiliation: f Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: g Department of Onco-Hematology, Division of Medical Oncology , Centro di Riferimento Oncologico della Basilicata, IRCCS , Rionero in Vulture (PZ) , Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Aieta
authors.affiliation: h Department of Translational Medical Sciences , University 'Federico II' , Naples , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Terracciano
authors.affiliation: d Division of Medical Oncology, Department of Uro-Gynaecological Oncology , Istituto Nazionale Tumori 'Fondazione G. Pascale' - IRCCS , Naples , Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Facchini
authors.affiliation: a Department of Clinical Medicine and Surgery , University Federico II of Naples , Naples , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Buonerba
authors.affiliation: i University of Alabama at Birmingham (UAB) Comprehensive Cancer Center , Birmingham , AL , USA.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
keywords: Kidney neoplasm; bevacizumab; monoclonal antibodies; nivolumab; targeted therapy