Table 3 In vivo CTC-derived xenograft models.

From: Functional analysis of circulating tumour cells: the KEY to understand the biology of the metastatic cascade

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]

  1. FACS fluorescent-activated cell sorting, CDX CTC-derived xenograft, TNBC triple-negative breast cancer, SNV single-nucleotide variant, NE neuroendocrine, MIC metastasis-initiator cells.
  2. This table summarises the different attempts to establish CTC-derived xenografts.