Table 3.

In vivo CTC-derived xenograft models.

Type of cancer	Isolation method	Injection procedure	Main results	Ref
Breast cancer	RosetteSep and FACS (PI- CD45-EpCAM + )	-Dilution in Matrigel - Injection in femoral medullar cavity	- Drug sensitivity not evaluated - Specific CTC MIC signature: EpCAM+CD44 + MET + CD47 + - decreased progression-free survival of patients with CD44 + , CD47 + and MET + CTCs	[36]
Breast cancer	Density gradient centrifugation: Histopaque®	- Dilution in Matrigel - Subcutaneous injection	- Drug sensitivity not evaluated - CDX model was representative of the primary tumour features: ER- PR- pan-CK + aECAD+ - identification of MELK as a prognostic marker of TNBC - WNT pathway upregulation as a potential therapeutic target in TNBC	[37]
Breast cancer	Multiparametric FACS (CD45-/CD34-/CD105-/CD90- CD73-)	- Intracardiac injection in aseptic conditions	- Distinct transcriptomic signatures between CTCs from primary tumour site in patients and the corresponding model - Survival analyses of transcriptome signature - Identification of 597 genes related to liver metastasis in TNBC	[20]
Small cell lung cancer	Ficoll-Paque density gradient and CD45 RosetteSep negative selection	- Dilution in Matrigel - Subcutaneous injection	- CDXs represent clinical SCLC - Drug sensitivity was evaluated and CDX mimicked the donor’s response to chemotherapy - CDX tumours reflect CTC genomic profile	[39]
Small cell lung cancer	Ficoll-Paque density gradient and CD45 RosetteSep negative Selection CTC-iChip	- Dilution in Matrigel - Subcutaneous injection	- Drug sensitivity evaluated - Correlation of MYC signatures with drug resistance by transcriptomic analysis - CDX mirrors the patient’s cancer progression	[40, 93]
Non-small cell lung cancer	Ficoll-Paque density gradient and CD45 RosetteSep negative selection	- Dilution in Matrigel - Subcutaneous injection	- Importance of mesenchymal CTCs with tumorigenic capacity - Absence of CTC-EpCAM(+) is not a limitation for metastasis formation	[41]
Prostate cancer	DLA/R Ficoll-Paque density gradient and CD45 RosetteSep negative selection	- Dilution in Matrigel - Subcutaneous injection	- Same genome characteristics in CTC, patient tumour, and CDX - Tumorigenic CTCs with acquired CRPC-NE features - Genomic alternations in CDX models	[43]
Melanoma	Ficoll-Paque density gradient and CD45 RosetteSep negative selection	- Dilution in Matrigel - Subcutaneous injection	- Drug sensitivity and patients’ response to treatment were evaluated - Concordance in SNV profiles - CTCs have similar tropism as the patient’s tumours	[44]

FACS fluorescent-activated cell sorting, CDX CTC-derived xenograft, TNBC triple-negative breast cancer, SNV single-nucleotide variant, NE neuroendocrine, MIC metastasis-initiator cells.

This table summarises the different attempts to establish CTC-derived xenografts.