Line 1 – Basic and Translational Oncology

Description

Study of the molecular, genetic and epigenetic mechanisms at the origin of the resistance of tumors to the main types of systemic treatment, such as molecular target therapy, anti-angiogenic therapy, immunotherapy. The research is conducted both at a pre-clinical level, using appropriate in vitro and murine tumor models, and by analyzing biological samples of patients treated with these drugs. It makes use of multi-omic and inter-disciplinary technological approaches.

Background

Experimental oncology has historically represented a fundamental incubator for the conception of current models of knowledge of tumor biology, summarized by the so-called “Hallmarks of cancer”, as well as the starting point for the development of innovative therapies for cancer that in the last decades have become available to a growing audience of cancer patients. Examples in this sense are provided by molecular targeting therapies for so-called operable genes, or by therapies that modulate the tumor microenvironment, such as anti-angiogenic therapy and immunotherapy, which collectively contribute to achieving precision oncology. One of the main challenges of this sector is currently that of translating this great wealth of knowledge into a measurable improvement of diagnostic and therapeutic perspectives for patients, combining observations that come from the pre-clinical world with others obtained directly from the clinic.

Rationale

Precision oncology is a booming area of ​​medicine made possible by: (i) increasing availability of molecular targets in tumors and of drugs designed around these targets and (ii) by the concrete possibility of identifying the genetic alterations that can be activated in tumors in an increasing number of patients. However, the therapeutic success of this approach risks to be undermined by the phenomenon of tumor heterogeneity and resistance to systemic therapies, the mechanisms of which are still insufficiently understood. There are already numerous recent examples that indicate that both basic research, using suitable in vitro or animal models, and translational research, based on the analysis of biological samples from patients, can provide innovative ideas for the implementation of precision oncology. and overcoming the resistance to treatment.
The IRCCSs are generally well placed to contribute to these developments, both by virtue of their technological endowment and the human capital they have. However, it is important to aggregate this know-how around priority and homogeneous themes capable of promoting intra- and inter-IRCCS interactions, also through the promotion of dedicated research programs. An example of this at the IOV came from the recent approval of a research program on liquid biopsy in oncology. As part of this program, various advanced molecular methods have been integrated for mutational profiling and the search for therapeutic targets with relevant clinical questions in oncology, with the ultimate goal of producing results that, in addition to scientific value, also have clinical relevance and can be used to improve patient care.

Global Goals

• Implementation of liquid biopsy for the identification of operable genetic alterations and dynamic monitoring of the therapeutic response in conditions of particular clinical relevance.
• Development of advanced technological platforms for the preclinical study of the mechanisms of resistance to anti-tumor drugs.
• Development of innovative preclinical models for the study of new therapeutic combinations capable of overcoming drug resistance.

Expected and measurable results over the three-year period

• Number of patents filed on issues relating to precision oncology (e.g. predictive response markers or resistance markers) and increase in the related royalties received.
• At least 50% increase over the previous three years in the number of spontaneous translational oncology studies at the IOV as coordinator of multicenter studies.
• Validation of at least one innovative liquid biopsy approach demonstrating clinical utility in a selected group of neoplastic patients.