Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

Lorena Incorvaia, Giuseppe Bronte, Viviana Bazan, Giuseppe Badalamenti, Sergio Rizzo, Gianni Pantuso, Clara Natoli and Antonio Russo _

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Oncotarget. 2016; 7:21259-21271. https://doi.org/10.18632/oncotarget.7267

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Lorena Incorvaia1,*, Giuseppe Bronte1,*, Viviana Bazan1,*, Giuseppe Badalamenti1, Sergio Rizzo1, Gianni Pantuso2, Clara Natoli3 and Antonio Russo1

1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy

2 Department of Surgical, Oncological and Oral Sciences, Section of Surgical Oncology, University of Palermo, Palermo, Italy

3 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy

* These authors have contributed equally to this work

Correspondence to:

Antonio Russo, email:

Keywords: renal cell cancer, tyrosine kinase inhibitor, mTOR, angiogenesis, VEGFr

Received: November 09, 2015 Accepted: January 29, 2016 Published: February 08, 2016


The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).

This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.

Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

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