Fidelity and stability of PDX models
| Reference | Tumor type | Original tumor-first passage | Subsequent passages |
|---|---|---|---|
| (28) | CRC | Conserved histopathology characteristics between donor and PDX models. | Stable CNA across passages. |
| Similarities in CNA between donor and PDX models. | |||
| Consistent KRAS, NRAS, BRAF, and PI3K mutation status. | |||
| (29) | CRC | Unsupervised clustering analysis using aCGH and GE shows that the donor tumors and PDX clustered together. | Stable aCGH and GE profile across passages. |
| 203 differentially expressed annotated genes correspond to stroma-related genes and pathways. | |||
| (31, 34) | HBC | Conserved IHC expression of ER, PR, and HER2. | Stable CNA and GE profile across passages. |
| Analysis of CNA showed 14/18 paired tumors–PDX shared more than 56% CNA. | Variations in stromal related genes. | ||
| 16/18 paired tumors–PDX clustered together in unsupervised hierarchical analysis. | |||
| PDX showed losses in 176 and gains in 202 chromosome regions compared with primary tumors. | |||
| Stable GE profile with less than 5% variations. | |||
| (30) | HBC | Conserved histopathology characteristics between donor and PDX models. | Stable IHC profile over time. |
| Conserved IHC expression for CK, E-cadherin, β-catenin, vimentin, ER, PR, and HER2. | |||
| Unsupervised clustering analysis using GE shows that donor tumors and PDX clustered together. | |||
| Maintenance in the pattern of CNA. | |||
| Intrinsic breast cancer subtypes concordant between the donor tumors and PDX. | |||
| (16) | HBC | Conserved histopathology characteristics between donor and PDX models. | Stable histopathologic and IHC expression. |
| Conserved IHC expression for CK, p53, Ki67, ER, PR, HER2, and EGFR. | Stable GE, RPPA, and SNP across passages. | ||
| Intrinsic breast cancer subtypes represented in PDX models. | |||
| (21) | NSCLC | Conserved histopathologic characteristics between donor and PDX models. | |
| Conserved IHC expression of Ki67 and EpCAM. | |||
| Unsupervised clustering analysis using GE shows the donor tumors and PDX clustered together with correlation coefficient ranging from 0.78 to 0.94. | |||
| 134 differentially expressed genes correspond to cell adhesion and immune response genes and pathways. | |||
| (26, 33) | PDAC | Concordance in mutations in KRAS and DPC4. | Concordance in gemcitabine response between F3 and F6. |
| Conserved GE profile (R2 = 0.69). | Enrichment in angiogenesis gene signature in F5. | ||
| (25) | SCC/SCCHN | Conserved histopathologic characteristics between donor and PDX models. | High correlation (R2 ∼ 0.94) in GE from F2-F4. |
| High correlation (R2 = 0.91) in EGFR expression. | Concordance in cetuximab response between F2 and F4. | ||
| High correlation (R2 ∼ 0.8) in GE. | |||
| Variation in immune-related pathways. | |||
| (15) | RCC | Conserved histopathologic characteristics. | Conserved histopathologic characteristics. |
| Donor and PDX models cluster together in unsupervised hierarchical clustering analysis using GE. | Serial passages clustered together in unsupervised hierarchical clustering analysis. | ||
| PDX retained CNA from the donor tumor. | Maintains CNA of the donor tumor. | ||
| Similar mutation landscape in NGS studies. |
NOTE: This table summarizes the data from different studies in which PDX models have been compared with donor tumors using a variety of methods.
Abbreviations: aCGH, comparative genomic hybridization array; CRC, colorectal cancer; GE, gene expression; HBC, human breast cancer; IHC, immunohistochemistry; NGS, next-generation sequencing, PR, progesterone receptor; RCC, renal cell cancer; RPPA, reverse phase protein array; SNP, single-nucleotide polymorphism; SCC, squamous cell carcinoma.