Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine.

Neoplasia : an International Journal for Oncology Research
Maria RiveraWolfgang Walther

Abstract

Patient-derived xenograft (PDX) tumor models represent a valuable platform for identifying new biomarkers and novel targets, to evaluate therapy response and resistance mechanisms. This study aimed at establishment, characterization and therapy testing of colorectal carcinoma-derived PDX. We generated 49 PDX and validated identity between patient tumor and corresponding PDX. Sensitivity of PDX toward conventional and targeted drugs revealed that 92% of PDX responded toward irinotecan, 45% toward 5-FU, 65% toward bevacizumab, and 61% toward cetuximab. Expression of epidermal growth factor receptor (EGFR) ligands correlated to the sensitivity toward cetuximab. Proto-oncogene B-RAF, EGFR, Kirsten rat sarcoma virus oncogene homolog gene copy number correlated positively with cetuximab and erlotinib sensitivity. The mutational analyses revealed an individual mutational profile of PDX and mainly identical profiles of PDX from primary tumor vs corresponding metastasis. Mutation in PIK3CA was a determinant of accelerated tumor doubling time. PDX with wildtype Kirsten rat sarcoma virus oncogene homolog, proto-oncogene B-RAF, and phosphatidylinositol-4,5-bisphosphate 3-kinaseM catalytic subunit alfa showed higher sensitivity toward cetux...Continue Reading

Citations

Jun 4, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Zhuanhuai WangLopa Mishra
Sep 30, 2021·Experimental and Therapeutic Medicine·Zhenyu YinHao Chen

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Methods Mentioned

BETA
xenograft
xenografts
Assay
Protein Assay
enzyme-linked immunosorbent assays
xenografting
PCR
ELISA
ubiquitination

Software Mentioned

Illumina GenomeStudio
StepOne
R
Graph Pad Prism
MaxQuant
SEA
StepOnePlus
Proteomics Toolset for Integrative Data Analysis ( Protigy
statistical
DAVID

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