title: New molecular targets in non clear renal cell carcinoma: An overview of ongoing clinical trials.
abstract: Non-clear cell renal cell carcinomas (nccRCCs) are a heterogeneous group of tumors, characterized by different histological features, molecular alterations, clinical outcomes, and responses to treatment. According to the 2004 WHO classification, 50 different histotypes were recognized. In 2013, five new distinct epithelial tumors and three provisional entities have been added to this classification, relying on morphology, immunohistochemistry, cytogenetics, and molecular pathology advances. Targeted therapies against VEGF and mTOR pathways have become the cornerstones of the treatment for clear cell RCC, dramatically revolutionizing the patients' prognosis. Interestingly, other than mTOR and VEGF pathways, tumor proliferation of some nccRCC histotypes seems to depend on alternative signaling pathways, as demonstrated by the close correlation between papillary RCC and activation of the HGF/MET axis. Currently, several strategies are under evaluation in patients with nccRCC. These approaches include TKIs and mTOR inhibitors, MET-pathway antagonists and immunotherapy. The aim of this review is to analyze the rationale for the use of TKIs and mTOR inhibitors as treatment options for nccRCC and to describe the future therapeutic perspectives for these patients.
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Clinica di Oncologia Medica, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126 Ancona, Italy. Electronic address: mattymo@alice.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.affiliation: Clinica di Oncologia Medica, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126 Ancona, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sotte
authors.affiliation: Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Conti
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Surgery, Cordoba University Medical School, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Scarpelli
authors.affiliation: Clinica di Oncologia Medica, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126 Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
mesh_terms: D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D015398:Signal Transduction
keywords: Clinical trials; Immunotherapy; Non clear cell renal cell carcinoma; Prognosis; Tyrosine kinase inhibitors