Identification of circulating biomarkers predictive of response to immunotherapies in patients with clear cell renal cell carcinoma

Project objectives

Soft tissue sarcomas are a heterogeneous group of rare solid tumors of mesenchymal origin. Surgical resection is the standard treatment for localized disease; however, approximately 50% of patients develop disease recurrence. The prognosis for patients with metastatic disease is severe, with an overall survival of approximately 12 months. Currently, systemic therapy (anthracyclines/ifosfamide and trabectedin) represents the only therapeutic option for these patients. However, despite an initial response to these chemotherapeutic agents, patients develop resistance mechanisms that inevitably lead to disease progression.

A preliminary analysis in silico A study conducted by our research group has identified several proteins associated with a poor prognosis in patients with metastatic soft tissue sarcoma. Our team has also demonstrated that these proteins may be involved in mechanisms of resistance to chemotherapy.

Our project aims to evaluate whether selective inhibition of these factors is able to reverse trabectedin resistance in cellular models of soft tissue sarcomas.

The specific objectives of the project are:

1) evaluate the effect of trabectedin on the proliferation of resistant sarcoma cell lines in combination with specific inhibitors of proteins identified as potential causes of resistance

2) identify the inhibitor that is most capable of reversing trabectedin resistance

3) confirm its specific action by silencing the gene encoding the inhibitor's target protein

4) evaluate the efficacy of the inhibitor in combination with trabectedin in xenograft mouse models in which trabectedin-resistant sarcoma cells were inoculated

Start and end date

January 2018 - ongoing

Project Manager

Prof. Giuseppe Tonini
Prof. Bruno Vincenzi
Dr. Francesco Pantano

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

Coordinating institution of the project

Università Campus Bio-Medico di Roma

Funding source(s).

PharmaMar SA - Plaza del Descubridor Diego de Ordás, 3, 28003, Madrid