Systematic integrated analysis of liquid biopsies from patients with solid tumors

Call Reference: 
SC1-BHC-02-2019
Short description of project idea : 
We are proposing a systematic, integrated analysis of liquid biopsy (circulating tumor cells, circulating cell-free DNA, and extracellular vesicles) on biological fluids from patients suffering from solid epithelial tumors and enrolled in different clinical studies. Our proposal aims to identify novel biomarkers that are predictive of patients’ response to the proposed therapies to ultimately improve patients’ stratification and identify novel combinatorial treatments based on the information obtained from liquid biopsies and outcome of patients subjected to the different therapeutic approaches.
We are proposing a systematic, integrated analysis of liquid biopsy (circulating tumor cells, circulating cell-free DNA, and extracellular vesicles) on biological fluids from patients suffering from solid epithelial tumors and enrolled in different clinical studies. Our proposal aims to identify novel biomarkers that are predictive of patients’ response to the proposed therapies to ultimately improve patients’ stratification and identify novel combinatorial treatments based on the information obtained from liquid biopsies and outcome of patients subjected to the different therapeutic approaches.
Health
Main areas of expertise: 
Research at CIBIO is focused on four major research programs i.e. Cancer Biology & Genomics, Cell & Molecular Biology, Microbiology & Synthetic Biology, and Neurobiology & Development. The PIs pursue their goals in the frame of a holistic view of basic biological processes and of their derangement in disease, trying to establish a "double edge" model to biomedical research, in which basic science co-exists with translational approaches. In particular, the groups involved in the project idea have a consolidated core expertise on: - Analysis of circulating tumor cell-free DNA - Characterization of circulating extracellular vesicles in biological fluids
Main objectives of the project and how will they be achieved: 
Title: 
Aims of the project
Description: 
- To isolate circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles (EVs) from liquid biopsies of oncological patients at the time of diagnosis, treatment, and follow up. State-of-art and proprietary technologies will be adopted to achieve this goal; - To extract DNA, RNA, and proteins from liquid biopsy specimens, from primary tumors, and (when available) from metastatic tissues of oncological patients; - To perform deep Next-Generation Sequencing (NGS) of extracted DNA and RNA molecules; - To detect proteins on the surface of EVs, including ultra-sensitive technologies developed in our labs; - To create a comprehensive databank and an integrated computational framework of qualitative and quantitative molecular data obtained from liquid biopsy specimens, from primary tumors, and (when available) from metastatic tissues of oncological patients; - To correlate molecular data with quality and efficacy of the adopted therapeutic regimens to identify the most effective therapeutic interventions and potential combinations; - To score and validate the improved effectiveness of resulting combined therapeutic interventions in vitro and in vivo pre-clinical models.
Challenges that may determine the impact of the project: 
Title: 
Challenges of the project idea
Description: 
Identification and characterization of tumor-released information found in liquid biopsy is an exploitable alternative for monitoring the evolution of the disease during the applied treatments. New strategies allowing a deeper and dynamic detection of biomarkers mirroring the heterogeneity of tumor cells can be a “signal” of the efficient response to a pharmacological treatment and can be used for optimization of combined therapeutic interventions. The expected impact of the study will relate with: - Identification of new biomarkers in liquid biopsy to allow improved stratifications of patients groups; - Correlation and rationale of the effectiveness of the specific therapeutic interventions; - Implementation of innovative technology platforms to be applied in liquid biopsy The challenges associated with this impact are: - Unmarked correlation between molecular features and patients’ stratification; - Variable response of oncological patients of the “same group” to the same therapeutic regimens.
Partners that have already expressed interest in the project and expected role: 
Title: 
Preliminary consortium
Description: 
We have already contacts with partners from Spain, in particular: - Academic institute with expertise on liquid biopsies and access to clinical specimens from patients with solid tumors - Company implementing a specific sensitive technology for the detection of nucleic acids in biological fluids
Profile of partners sought and expected role: 
Title: 
Partners sought
Description: 
Expected partners of the project will have to address : - Clinical research institutes with access to oncological biobanks and databanks - Expertise on liquid biopsies - Companies with high-throughput technologies and expertise
Specific countries/regions/cities you are keen to collaborate with: 
No restrictions
First Name: 
Vito
Last Name: 
D'Agostino
Name of the organisation: 
Centre for Integrative Biology, University of Trento
Short description of organisation: 
CIBIO, founded in 2007, is a cutting-edge and top-ranked academic biomedicine institute within the University of Trento, organised as a hybrid research centre/university department, taking the best from either model. The Centre has recently grown to 34 Research Laboratories headed by successful and independent Principal Investigators of Italian, Swiss, French, Belgian and American nationality, and is expected to expand to become a Department by the end of 2017 on the premises of strategic local funding from the Autonomous Province of Trento and the University. The Centre is at the top of rankings for quality of the research among National academic institutes in the area of Biological Sciences (ANVUR 2011-2014). CIBIO provides a high level of research services and Core Facilities, operated by highly skilled staff scientists, with all the state-of-the-art equipment and tools necessary in supporting Labs biomedical research projects to be carried out with the required level of technological sophistication.

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