The BiLiGeCT project, focused on liquid biopsies for the Clinical Management of Tumors, has been awarded a prestigious funding from the MIUR's National Operational Program (PON). Aging, chronic and degenerative diseases, and quality of life are the three key factors identified as priority areas in the "Health" sector of the national strategic agenda. The project, titled "Liquid Biopsies for the Clinical Management of Tumors" (acronym: BiLiGeCT), proposed by Cogentech, a Benefit Company of IFOM, in collaboration with the National Interuniversity Consortium for Innovative Synthesis Methodologies and Processes (CINMPIS, involving the University of Catania and the University of Messina), the Italian National Institute of Health (ISS), the University of Turin (UniTO), the Mediterranean Oncological Institute (IOM), and CaReBios, aims to improve the clinical management of oncological diseases. The ambitious BiLiGeCT project has secured funding from the National Operational Program for Research and Innovation 2014-2020, managed by the Ministry of Education, Universities and Research (MIUR). BiLiGeCT proposes innovative research to develop new and improved technological solutions to address two crucial aspects in the field of oncology: early diagnosis and therapeutic appropriateness.
Regarding the first point, the project focuses on the emerging issue of specific types of tumors, primarily resulting from population aging. Cancer is increasingly considered a disease associated with aging, and the project is based on the concept that early diagnosis almost always leads to better disease outcomes.
Regarding the second point, next-generation oncological therapies aim to transform tumors into chronic diseases. This is evidenced by the fact that continuous administration of the appropriate drug is required to control the disease.
Finally, the quality of life of cancer patients assumes an increasingly important role, considering the concept of chronicization of the disease. Patient associations also emphasize this aspect.
The project aims to address these objectives using an innovative tool, liquid biopsy, which holds promise as a new and more effective approach for the clinical management of tumors. In addition to traditional tissue biopsies, liquid biopsy involves minimally or non-invasive collection of biological fluids such as urine, oral washes, or primarily blood. Sophisticated molecular technologies are then used to detect various biomarkers indicative of the presence of a tumor. Liquid biopsy is well-suited for "longitudinal studies" that involve collecting biological samples at different time points during the clinical and instrumental surveillance program, enabling the monitoring of the dynamic evolution of cancer over time. Therefore, liquid biopsy not only aids in diagnosis but also allows for adapting therapy over time by following the molecular changes that occur during the disease's progression.
Through a liquid biopsy approach, the BiLiGeCT project aims to address specific questions related to early diagnosis in healthy individuals with a high genetic risk of tumors, particularly those with hereditary/familial BRCA (1 and 2) gene mutations. The objective is to develop a more sensitive, effective, and cost-efficient diagnostic tool compared to current instrumental screening methods.
The second line of research, similar to the first, focuses on individuals with a previous history of tumors in the context of hereditary/familial BRCA-related cancers. The aim is to identify tumor recurrence early and characterize it molecularly to monitor the effectiveness and appropriateness of therapy.
The third line of research focuses on early diagnosis using liquid biopsies, following similar approaches as described for hereditary/familial tumors, but specifically targeting lung and prostate cancers. The objective is to make disease diagnoses more effective and less invasive while introducing technological innovations for molecular diagnosis and prognosis of these tumors.
The fourth line of research will address the issue of early diagnosis, especially in the case of metastatic disease recurrence and the choice based on the molecular profile of the evolving disease during second-line treatment and beyond in colorectal tumors.
The fifth line of research aims to develop an innovative cellular test for screening new therapeutically active molecules or the repositioning of already known drugs for mutations in the BRCA genes and those genetic elements that collaborate with them to ensure the integrity of DNA through its repair mechanisms (BRCAness). These drugs, in general, belong to the category of so-called PARP enzyme system inhibitors. These inhibitors have been found to be effective not only for hereditary-familial tumors with the aforementioned germline mutations but also for sporadic tumors of the same histotype with somatic mutations in these genes. With this functional model, the problem posed by BRCA mutations of unknown functional significance (VUS) will also be addressed. These mutations will be tested for their sensitivity to PARP inhibitors active on tumors with clearly pathogenic BRCA mutations.
The ultimate goal of the project is rightly ambitious and is at the forefront of current technology. However, it appears feasible thanks to the infrastructure and previous experience in the use of innovative technologies of the participating institutions and the qualified expertise available within them. Furthermore, an undeniable added value is provided by the availability of a cohort of healthy individuals or those with previous experience of tumor disease belonging to the population at genetic risk of developing breast and/or ovarian cancer because they carry a germline mutation in one of the BRCA genes. This opportunity appears unique for the diagnostic objectives of liquid biopsy, both because the type of tumor that will appear can be predicted "a priori" due to its characteristic of earliness, and because several molecular aspects of the tumors in question are well-known and will allow the development of highly personalized molecular diagnostic tools for these patients.
Additionally, with the liquid biopsy approach, it will be possible to monitor the cost-effectiveness of the introduction of these new diagnostic methodologies.
The successful achievement of the project's final objectives will allow for the introduction of both innovative laboratory techniques and original diagnostic assays in the market.