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Clonal tracking in cancer and metastasis

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The eradication of many cancers has proven challenging due to the presence of functionally and genetically heterogeneous clones maintained by rare cancer stem cells (CSCs), which contribute to disease progression, treatment refractoriness, and late relapse. The characterization of functional CSC activity has necessitated the development of modern clonal tracking strategies. This review describes viral-based and CRISPR-Cas9-based cellular barcoding, lineage tracing, and imaging-based approaches. DNA-based cellular barcoding technology is emerging as a powerful and robust strategy that has been widely applied to in vitro and in vivo model systems, including patient-derived xenograft models. This review also highlights the potential of these methods for use in the clinical and drug discovery contexts and discusses the important insights gained from such approaches.

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Data Availability

Data availability does not apply to this article since no new data were generated or analyzed in this review.

Abbreviations

Cre:

Cre recombinase

CreER:

Cre recombinase to estrogen receptor

CSC:

Cancer stem cells

CML:

Chronic myeloid leukemia

CRISPR:

Clustered regularly interspaced short palindromic repeats

Cas9:

CRISPR-associated protein 9

EGFR:

Epidermal growth factor receptor

gRNA:

guide RNA

hgRNA:

homing guide RNA

NGS:

Next-generation sequencing

NSCLC:

Non-small cell lung cancer

PCR:

Polymerase chain reaction

scRNA-seq:

single-cell RNA sequencing

sgRNA:

single-guide RNA

seqFISH:

sequential small-molecule fluorescent in situ hybridization

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Funding

The authors were supported in part by grants to N.K. from the Mayo Clinic Breast Cancer SPORE (CA116201-12CEP) and the Mayo Clinic Ovarian Cancer SPORE (P50 CA136393-DRP). M.R. was supported by the NIH T32 grant. L.V.N. was supported by the ESMO Translational Research Fellowship and the Conquer Cancer ASCO Young Investigator Award.

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  1. Musheer Aalam and Long Viet Nguyen contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA

    Syed Mohammed Musheer Aalam, Megan L. Ritting & Nagarajan Kannan

  2. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

    Long Viet Nguyen

  3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Long Viet Nguyen

  4. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Long Viet Nguyen

  5. Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA

    Nagarajan Kannan

  6. Center for Regenerative Biotherapeutics, Mayo Clinic, Rochester, MN, USA

    Nagarajan Kannan

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  1. Syed Mohammed Musheer Aalam
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  4. Nagarajan Kannan
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SMA and LN prepared the draft of the manuscript. SMA and MR prepared the figures and tables for the manuscript. NK conceptualized, supervised, and finalized the manuscript.

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Correspondence to Nagarajan Kannan.

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Aalam, S.M.M., Nguyen, L.V., Ritting, M.L. et al. Clonal tracking in cancer and metastasis. Cancer Metastasis Rev 43, 639–656 (2024). https://doi.org/10.1007/s10555-023-10149-4

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