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Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models

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NIAID Data Ecosystem2026-03-11 收录
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https://www.ncbi.nlm.nih.gov/bioproject/PRJNA596887
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Molecular mechanisms for secondary resistance (SR) in colorectal cancers (CRCs) under anti-EGFR therapy are largely derived from circulating tumor DNA (ctDNA) and rarely from primary tissue. Here we generated anti-EGFR SR tumors from ten KRAS, NRAS, BRAF, and PI3K wild-type CRC patient derived xenograft (PDX) models and characterized these by whole exome sequencing. We found an unexpected low driver mutations frequency (26%) in SR tumors. However, transcriptomic analyses revealed a strikingly high frequency of RAS-MEK-ERK pathway reactivation via transcriptional reprogramming.
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2019-12-20
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