Patient-Derived Xenograft

Overview

Patient-derived xenograft (PDX) models are established by directly implanting tumor fragments or dissociated cells from patient biopsies into immunodeficient mice (commonly NOD-SCID, NSG, or nude). Unlike cell-line-derived xenografts (CDX), PDX models retain the histologic architecture, genomic heterogeneity, and stromal microenvironment of the original tumor, making them more predictive of clinical drug response. PDX models are used for preclinical drug efficacy testing, biomarker validation, and co-clinical trial design.

Used by

• Four mCRPC PDX lines (#546, #1092, #1102, #1267) in NOD-SCID mice used to test olaparib + spautin-1 (USP10 inhibitor) combination therapy; PDX#546 and PDX#1092 (high TRMT10A/USP10 expression) showed additive-to-synergistic tumor growth suppression versus olaparib alone (PDX#1092: 42.9% additional volume reduction), with elevated cleaved caspase-3, cleaved PARP, and γ-H2AX in tumor lysates PMID:28068672.
• Used patient-derived xenograft (PDX) models to evaluate therapeutic response in vivo PMID:28196596

Notes

• PDX selection was based on high TRMT10A and USP10 IHC expression, demonstrating biomarker-directed preclinical model selection.
• PDX models were implanted in NOD-SCID mice and treated when tumors reached palpable size.
• Tolerability in C57BL/6 mice confirmed no additional hematologic toxicity beyond olaparib monotherapy.

Sources

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