PREDICT

 

 

The most prevalent approach of molecular oncology focuses on the analysis of the entire tumor mass and identifies profiles of the genetic variants of neoplasms arising from both healthy and neoplastic cells. Genomics, epigenomics and gene expression in colorectal cancer (CRC) have not been exhaustively studied at the level of a single cell. Single-cell (SC) analysis of tumors has proven cellular heterogeneity in various cancers, and it is now technically possible to trace each neoplastic clone, but SC methodology is not yet a widespread methodology. For adequately study intra-tumor heterogeneity, it is necessary to analyze hundreds of SCs derived from CRCs and mucosal normal colic from the same patient. Recent analyses reveal extensive mutational diversification acquired during clonal expansion of the tumor and the simultaneous absence of this process in normal mucosa, with a different correlation in drug response even among neoplastic cells from the same site. The diversification of CRC is accompanied by widespread, stable and inherited differences in the biology of tumor SCs. The application of sophisticated “single-cell multiomics” sequencing (scNGS) together with sampling of different areas of the tumor primary, analysis of lymphatic tissue metastases and distant metastases, and comparison with healthy tissue, will enable important results on intra-tumor heterogeneity and response to therapy. The combined use of these revolutionary technologies is showing relevant preliminary results related to pharmacological sensitivity dependent on cellular variability. This project proposes the use of the scNGS technique to identify heterogeneity intra-tumor and improve therapeutic response and recurrence in a sample with high clinical and genomics, which will achieve a deep level of resolution.

Funding sources:

Fondo di Beneficenza, Intesa Sanpaolo S.p.A. (Milano, IT) - GRANT_NUMBER: B/2020/0094

Research Team:

The project is coordinated by Andrea Angius and the team members work at the Institute of Genetic and Biomedical Research (IRGB) and at the Department of Medical, Surgical and Experimental Sciences at the University of Sassari.