Effects of new molecular target therapies for renal carcinoma on bone tumor microenvironment

Project objectives

Several molecularly targeted drugs have recently been approved for the treatment of metastatic clear cell renal cell carcinoma. All of these drugs have strong inhibitory activity at several receptor tyrosine kinases, including MET and vascular endothelial growth factor receptors (VEGFR), cellular signaling pathways that support tumor progression, metastasis development, and angiogenesis. It is well known that bone is one of the most common sites of renal cell carcinoma metastasis, and patients with bone metastases develop serious skeletal-related complications over time.

Data published in the literature have shown that these receptors are expressed by cells in the bone microenvironment and, therefore, may play a key role in osteoblastic and osteoclastic differentiation and activity and in the regulation of bone homeostasis. Furthermore, several preclinical studies on models of bone metastasis suggest that the bone microenvironment represents a potential mediator of responses to treatment with tyrosine kinase inhibitors. To date, it is still unclear whether treatment with these inhibitors has a direct effect on bone cells and how this modulation of the microenvironment influences tumor growth in the bone.

The specific objectives of the project are:

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

2) investigate a possible indirect, osteoblast-mediated antitumor effect of tyrosine kinase inhibitors

3) evaluate the direct antitumor effect of tyrosine kinase inhibitors on models of renal cell carcinoma bone metastasis

Start and end date

June 2017 - ongoing

Project Manager

Prof. Giuseppe Tonini
Prof. Daniele Santini
Dr. Francesco Pantano

Research Team:
- Dr. Michele Iuliani
- Dr. Giulia Ribelli
- Dr. Sonia Simonetti

Coordinating institution of the project

Università Campus Bio-Medico di Roma

Funding source(s).

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

Eisai Italia Srl - Via Giovanni Spadolini, 5, 20141 Milan MI