title: Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma.
abstract: 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.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Badalamenti
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Surgical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Pantuso
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents
keywords: VEGFr; angiogenesis; mTOR; renal cell cancer; tyrosine kinase inhibitor