Project Objectives

Several target therapies have recently been approved for the treatment of metastatic clear cell renal cell carcinoma. These drugs have a strong inhibitory activity for several tyrosine kinase receptors, including MET and vascular endothelial growth factor receptors (VEGFR), molecular pathways involved in tumor progression, metastasis development and angiogenesis. It is known that bone is one of the more frequent site of metastasis from renal carcinoma and that patients suffering from bone metastases develop serious skeletal complications over time. Data published in the literature showed that MET and VEGFR are expressed by osteoclasts and osteoblasts and play a key role in their differentiation and activity regulating bone homeostasis. Furthermore, several pre-clinical studies on bone metastasis models suggest that the bone microenvironment is a potential mediator of responses to treatment with tyrosine kinase inhibitors. To date, it has not yet been clarified whether treatment with these inhibitors has a direct effect on bone cells and how this modulation of the microenvironment influences tumor growth in bone.

The specific objectives of the project are:

1) to analyze the direct effects of tyrosine kinase inhibitors on primary human osteoblasts and osteoclasts differentiation and activity

2) to investigate a possible indirect antitumor effect of tyrosine kinase inhibitors mediated by osteoblasts

3) to evaluate the direct antitumor effect of tyrosine kinase inhibitors on bone metastases models of renal carcinoma.

Start/End Date

June 2017 – ongoing

Principal Investigators

Prof. Giuseppe Tonini

Prof. Daniele Santini

Dr. Francesco Pantano

Research Team

Dr. Michele Iuliani

Dr. Giulia Ribelli

Dr. Sonia Simonetti

Host Institution

Campus Bio-Medico University of Rome

Other Institutions involved

None

Source of funding

Ipsen Italia Spa - Via del Bosco Rinnovato, 6, 20090 Assago MI

Eisai Italia S.r.l. - Via Giovanni Spadolini, 5, 20141 Milano MI