Project description:In this study we want present a bank of metastatic colorectal cancer (mCRC) Patient Derived Organoids (PDOs) obtained from Patient Derived Xenografts (PDXs). These models are annotated with different omics to advance our understanding of CRC. We wanted to create a resource for the scientific community to assess the predictive reliability of these preclinical models. We performed comparative analyses between PDOs and matched PDXs to assess the similarities of these two platforms regarding molecular profiles and transcriptional classification. Moreover, we analyzed how these models respond to Cetuximab, a chimeric monoclonal antibody, normally given to patients after chemotherapy, that inhibits EGFR. After having assessed models’ reliability with Cetuximab, we aimed at identifying potential synergistic drugs to individuate new possible therapeutic prospects.
Project description:Recent work built on published transcriptional subtypes of colorectal cancer (CRC) has shown that tumor stromal content impacts CRC classification, with both clinical and biological implications. To Tackle the issue of intrinsic epithelial gene profiles, we assembled a dataset of matched liver metastatic colorectal cancer and Patients Derived Xenografts. in which the stroma of the original tumor is substituted by murine tissue, we deployed a molecularly annotated collection of 515 PDXs from 244 patients as a resource for species (human)-specific assessment of cancer-cell intrinsic transcriptional features. We identified five ColoRectal cancer Intrinsic Subtypes (CRIS) endowed with functional and phenotypic characteristics related to specific genetic traits, most of which were not evidenced in the transcriptional subgroups reported in previous studies.
Project description:Recent work built on published transcriptional subtypes of colorectal cancer (CRC) has shown that tumor stromal content impacts CRC classification, with both clinical and biological implications. To Tackle the issue of intrinsic epithelial gene profiles, we assembled a dataset of matched liver metastatic colorectal cancer and Patients Derived Xenografts. in which the stroma of the original tumor is substituted by murine tissue, we deployed a molecularly annotated collection of 515 PDXs from 244 patients as a resource for species (human)-specific assessment of cancer-cell intrinsic transcriptional features. We identified five ColoRectal cancer Intrinsic Subtypes (CRIS) endowed with functional and phenotypic characteristics related to specific genetic traits, most of which were not evidenced in the transcriptional subgroups reported in previous studies.