The PRO-ACTIVE study aims to develop a clinical-translational program in the field of cancer prevention in all its phases (primary, secondary, and tertiary) to intervene before the clinical and radiological manifestation of the disease. It starts with risk prediction and leads to early diagnosis of the disease or recurrence in the subclinical phase.
The PRO-ACTIVE study includes the following activities:
* WP1: Integrated DNA-RNA approach for the identification of hereditary markers of predisposition to tumors * WP2: Global biological and molecular analysis of the host and tumor for the prevention and monitoring of recurrences * WP3: Analysis of the immunological status for the diagnosis of primary prevention and relapses in correlation to genetic and environmental factors * WP4: Study of the tumor microenvironment for recurrence prediction
Age >18 years;
Patients with breast cancer, including patients who meet the AIOM criteria for eligibility for BRCA testing and patients with lobular breast cancer;
Patients with radically resected colon cancer, including patients with stage III colon cancer and vascular invasion;
Patients with ovarian carcinomas;
Age <18 years;
Unwillingness or inability to give informed consent
600 patients known to have breast cancer (N=200), ovarian cancer (N=200) and colon cancer (N=200) will be evaluated. Based on the results of the germline genetic test, patients will be classified into three cohorts: * COHORT 2A, individuals who are carriers of hereditary traits (probands) * COHORT 2B, subjects identified by genetic counselling as being at risk of being carriers of hereditary neoplastic syndrome, not confirmed by genetic testing * COHORT 2C, an additional subgroup of patients (N=150), 50 for each type of tumour, who tested negative in diagnostic genetic analysis. COHORT 3 includes 250 patients who underwent radical surgery: * locally advanced breast cancer with triple-negative phenotype or lobular histology * high-grade serous ovarian cancer * metastatic melanoma * stage IIB and IIIA non-small cell lung cancer * colon cancer with lymph node involvement and vascular invasion
Case-only
Other
Not listed
Number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
Patients will undergo blood sampling for the extraction of nucleic acids (DNA and RNA) to determine number, frequency and type of genetic variants in known genes not detected by routine diagnostic tests for hereditary tumours
Number of isolated circulating tumour cells (CTCs) in patients' blood
The aim of this outcome is the correlation between the number of isolated circulating tumour cells (CTCs) and the clinical outcome
Amount of circulating tumour DNA (ctDNA) in patients' blood
The aim of this outcome is the correlation between the detection of circulating tumour DNA (ctDNA) and the clinical outcome
Qualitative outcomes: Characterisation of the level of differentiation and clonal heterogeneity of the T lymphocyte repertoire in the context of different tumours
Patients who will undergo standard preoperative drug treatment will also have blood samples taken before the start of treatment and before surgery. The collected material will undergo the following analyses: * Phenotypic study using multiparametric cytometry of lymphocyte subpopulations. * Transcriptional profiling using sc-RNA sequencing (scRNA-seq) and surface markers * Longitudinal flow cytometric analysis of the specific response of tumour-infiltrating and peripheral T lymphocytes against tumour neoepitopes. * Single-cell multiomics analysis of the T lymphocyte response to specific neoepitopes identified in the tumour. * Study of chromatin structure in different subpopulations of TILs in patients with or without neoplastic progression. * Evaluation of the functional activation profile, memory properties, epigenetic profile, and inter- and intra-clonal heterogeneity
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