Publications by authors named "L Trusolino"
Article Synopsis
- * The study focuses on 231 colorectal cancer PDXs, analyzing their genetic and molecular profiles, and how they respond to the drug cetuximab, which targets EGFR in metastatic cancer.
- * Researchers developed a predictive model named CeSta that utilizes multi-omic data from PDXs to forecast cetuximab sensitivity, demonstrating better accuracy than traditional models based on cancer cell lines and offering promise for future therapeutic biomarker identification.
The breadth and depth at which cancer models are interrogated contribute to the successful clinical translation of drug discovery efforts. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, where experimental therapies are typically tested. Here we introduce XENTURION, an open-science resource offering a platform of 128 PDX models from patients with metastatic CRC, along with matched PDX-derived tumoroids.
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- * The study utilized a drug repurposing strategy and conducted experiments on CRC cells and patient-derived organoids to test the effects of AT9283, a known multitargeted kinase inhibitor.
- * Results showed that AT9283 effectively lowered MKK3 levels, inhibited cancer cell growth and motility, and was well-tolerated by normal colon cells, indicating its potential as a therapeutic option for advanced CRC by disrupting the MKK3/AURKA interaction.
HER2 amplification occurs in approximately 5% of colorectal cancer (CRC) cases and is associated only partially with clinical response to combined human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR)-targeted treatment. An alternative approach based on adoptive cell therapy using T cells engineered with anti-HER2 chimeric antigen receptor (CAR) proved to be toxic due to on-target/off-tumor activity. Here we describe a combinatorial strategy to safely target HER2 amplification and carcinoembryonic antigen (CEA) expression in CRC using a synNotch-CAR-based artificial regulatory network.
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