Cancer Stem Cell-Based Models of Colorectal Cancer Reveal Molecular Determinants of Therapy Resistance

摘要: UNLABELLED Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered prototype stem cell (CSC)-driven tumor, effects both and targeted therapies CSC compartment are largely unknown. We have optimized protocol for colorectal isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, high efficiency. was followed by vitro vivo validation, genetic characterization, drug sensitivity analysis, thus generating panels lines defined patterns mutations sensitivity. were polyclonal maintained intratumor heterogeneity terms somatically acquired differentiation state. Such used investigate generate proteomic picture signaling pathways implicated sensitivity/resistance anti-EGFR propose as sound preclinical framework test identify novel determinants resistance. SIGNIFICANCE cells (CSCs) been shown be responsible propagation, metastatic dissemination, relapse. However, molecular present CSCs, well mechanisms resistance, mostly Taking advantage genetically characterized derived tumors, this study provides an extensive analysis response EGFR-targeted overview factors or Furthermore, implementation biobank molecularly annotated innovative resource future investigations cancer.