Biology, vulnerabilities and clinical applications of circulating tumour cells

Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7–33 (2022).

Article  Google Scholar 

Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883–892 (2012). This large-scale next-generation sequencing study demonstrates a high degree of tumour heterogeneity not captured by single tumour biopsies, with consequences for therapy failure.

Article  CAS  Google Scholar 

Pantel, K. & Alix-Panabieres, C. Liquid biopsy and minimal residual disease - latest advances and implications for cure. Nat. Rev. Clin. Oncol. 16, 409–424 (2019).

Article  CAS  Google Scholar 

Ignatiadis, M., Sledge, G. W. & Jeffrey, S. S. Liquid biopsy enters the clinic - implementation issues and future challenges. Nat. Rev. Clin. Oncol. 18, 297–312 (2021).

Article  Google Scholar 

Alix-Panabieres, C. & Pantel, K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 11, 858–873 (2021).

Article  CAS  Google Scholar 

Mohme, M., Riethdorf, S. & Pantel, K. Circulating and disseminated tumour cells - mechanisms of immune surveillance and escape. Nat. Rev. Clin. Oncol. 14, 155–167 (2017).

Article  CAS  Google Scholar 

Lin, D. et al. Circulating tumor cells: biology and clinical significance. Signal. Transduct. Target. Ther. 6, 404 (2021).

Article  CAS  Google Scholar 

Bidard, F. C. et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 15, 406–414 (2014).

Article  Google Scholar 

Smerage, J. B. et al. Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J. Clin. Oncol. 32, 3483–3489 (2014).

Article  CAS  Google Scholar 

Cabel, L. et al. Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial. Br. J. Cancer 124, 1207–1213 (2021).

Article  CAS  Google Scholar 

Belderbos, B. P. S. et al. Associations between AR-V7 status in circulating tumour cells, circulating tumour cell count and survival in men with metastatic castration-resistant prostate cancer. Eur. J. Cancer 121, 48–54 (2019).

Article  CAS  Google Scholar 

Isebia, K. T. et al. CABA-V7: a prospective biomarker selected trial of cabazitaxel treatment in AR-V7 positive prostate cancer patients. Eur. J. Cancer https://doi.org/10.1016/j.ejca.2022.09.032 (2022).

Article  Google Scholar 

Sobin, L. H., Gospodarowicz, M. K. & Wittekind, C. TNM Classification of Malignant Tumours (John Wiley & Sons, 2011).

Nguyen, D. X., Bos, P. D. & Massague, J. Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9, 274–284 (2009).

Article  CAS  Google Scholar 

Lambert, A. W., Pattabiraman, D. R. & Weinberg, R. A. Emerging biological principles of metastasis. Cell 168, 670–691 (2017).

Article  CAS  Google Scholar 

Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114–1117 (2010).

Article  CAS  Google Scholar 

Ding, L. et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464, 999–1005 (2010).

Article  CAS  Google Scholar 

Haffner, M. C. et al. Tracking the clonal origin of lethal prostate cancer. J. Clin. Invest. 123, 4918–4922 (2013).

Article  CAS  Google Scholar 

Hosseini, H. et al. Early dissemination seeds metastasis in breast cancer. Nature 540, 552–558 (2016). This study demonstrates early dissemination and seeding of metastasis using mouse models, indicating that CTC circulation is likely to be a very early event in cancer progression.

Article  CAS  Google Scholar 

Schmidt-Kittler, O. et al. From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc. Natl Acad. Sci. USA 100, 7737–7742 (2003).

Article  CAS  Google Scholar 

Hüsemann, Y. et al. Systemic spread is an early step in breast cancer. Cancer Cell 13, 58–68 (2008).

Article  Google Scholar 

Rhim, A. D. et al. EMT and dissemination precede pancreatic tumor formation. Cell 148, 349–361 (2012).

Article  CAS  Google Scholar 

Klein, C. A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer 9, 302–312 (2009).

Article  CAS  Google Scholar 

Harper, K. L. et al. Mechanism of early dissemination and metastasis in Her2+ mammary cancer. Nature 540, 588–592 (2016).

Article  CAS  Google Scholar 

Hong, W. S., Shpak, M. & Townsend, J. P. Inferring the origin of metastases from cancer phylogenies. Cancer Res. 75, 4021–4025 (2015).

Article  CAS  Google Scholar 

Kim, M.-Y. et al. Tumor self-seeding by circulating cancer cells. Cell 139, 1315–1326 (2009). This is an elegant study demonstrating that cancer dissemination is not unidirectional and that CTCs home back to the lesions from where they came, with important prognostic ramifications.

Article  Google Scholar 

Naxerova, K. & Jain, R. K. Using tumour phylogenetics to identify the roots of metastasis in humans. Nat. Rev. Clin. Oncol. 12, 258–272 (2015).

Article  CAS  Google Scholar 

Schwartz, R. & Schaffer, A. A. The evolution of tumour phylogenetics: principles and practice. Nat. Rev. Genet. 18, 213–229 (2017).

Article  CAS  Google Scholar 

Cleary, A. S., Leonard, T. L., Gestl, S. A. & Gunther, E. J. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers. Nature 508, 113–117 (2014).

Article  CAS  Google Scholar 

Hong, M. K. et al. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat. Commun. 6, 6605 (2015).

Article  CAS  Google Scholar 

McFadden, D. G. et al. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156, 1298–1311 (2014).

Article  CAS  Google Scholar 

Zhao, Z. M. et al. Early and multiple origins of metastatic lineages within primary tumors. Proc. Natl Acad. Sci. USA 113, 2140–2145 (2016).

Article  CAS  Google Scholar 

Gundem, G. et al. The evolutionary history of lethal metastatic prostate cancer. Nature 520, 353–357 (2015). This seminal study demonstrates that tumour metastasis occurs not only from primary tumours but also from metastasis.

Article  CAS  Google Scholar 

Maddipati, R. & Stanger, B. Z. Pancreatic cancer metastases harbor evidence of polyclonality. Cancer Discov. 5, 1086–1097 (2015).

Article  CAS  Google Scholar 

Aceto, N. et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158, 1110–1122 (2014). We demonstrate for the first time that CTC clusters derive from oligoclonal primary tumour cell groupings and that they possess both superior survival and metastatic potential compared with that of individual CTCs.

Article  CAS  Google Scholar 

Cheung, K. J. et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc. Natl Acad. Sci. USA 113, E854–E863 (2016).

Article  CAS  Google Scholar 

Liu, X. et al. Homophilic CD44 interactions mediate tumor cell aggregation and polyclonal metastasis in patient-derived breast cancer models. Cancer Discov. 9, 96–113 (2019).

Article  Google Scholar 

Bockhorn, M., Jain, R. K. & Munn, L. L. Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed. Lancet Oncol. 8, 444–448 (2007).

Article  CAS  Google Scholar 

Follain, G. et al. Fluids and their mechanics in tumour transit: shaping metastasis. Nat. Rev. Cancer 20, 107–124 (2020).

Article  CAS  Google Scholar 

Follain, G. et al. Hemodynamic forces tune the arrest, adhesion, and extravasation of circulating tumor cells. Dev. Cell 45, 33–52 e12 (2018).

Article  CAS  Google Scholar 

Donato, C. et al. Hypoxia triggers the intravasation of clustered circulating tumor cells. Cell Rep. 32, 108105 (2020). Our laboratory demonstrates that hypoxic conditions favour the formation and intravasation of CTC clusters with enhanced metastatic potential, and that this can be targeted with proangiogenic agents.

Article  CAS  Google Scholar 

Zhang, H. et al. HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 31, 1757–1770 (2012).

Article  CAS  Google Scholar 

Jin, F., Brockmeier, U., Otterbach, F. & Metzen, E. New insight into the SDF-1/CXCR4 axis in a breast carcinoma model: hypoxia-induced endothelial SDF-1 and tumor cell CXCR4 are required for tumor cell intravasation. Mol. Cancer Res. 10, 1021–1031 (2012).

Article  CAS  Google Scholar 

Mazzone, M. et al. Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 136, 839–851 (2009).

Article  CAS  Google Scholar 

Harney, A. S. et al. Real-time imaging reveals local, transient vascular permeability, and tumor cell intravasation stimulated by TIE2hi macrophage-derived VEGFA. Cancer Discov. 5, 932–943 (2015).

Article  CAS  Google Scholar 

Rossi, M. et al. PHGDH heterogeneity potentiates cancer cell dissemination and metastasis. Nature 605, 747–753 (2022).

Article  CAS  Google Scholar 

Rodriguez-Tirado, C. et al. NR2F1 is a barrier to dissemination of early stage breast cancer cells. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-21-4145 (2022).

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