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.
Cancer Treat Rev. 2015 Jul;41(7):614-22. doi: 10.1016/j.ctrv.2015.05.006. Epub 2015 May 15.
Ciccarese C1, Massari F1, Santoni M2, Heng DY3, Sotte V4, Brunelli M5, Conti A6, Cheng L7, Lopez-Beltran A8, Scarpelli M9, Cascinu S4, Tortora G1, Montironi R9.
1 Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
2 Clinica di Oncologia Medica, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126 Ancona, Italy.
3 Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
4 Clinica di Oncologia Medica, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, via Conca 71, 60126 Ancona, Italy.
5 Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
6 Dipartimento di Scienze Cliniche e Specialistiche, Sezione di Urologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
7 Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
8 Department of Surgery, Cordoba University Medical School, Cordoba, Spain.
9 Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.