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Dis Model Mech. 2014 Jul;7(7):755-62. doi: 10.1242/dmm.015842.

Zebrafish as a model to assess cancer heterogeneity, progression and relapse.

Author information

1
Department of Molecular Pathology, Regenerative Medicine and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA. Harvard Stem Cell Institute, Cambridge, MA 02139, USA.
2
Department of Molecular Pathology, Regenerative Medicine and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA. Harvard Stem Cell Institute, Cambridge, MA 02139, USA. dlangenau@mgh.harvard.edu.

Abstract

Clonal evolution is the process by which genetic and epigenetic diversity is created within malignant tumor cells. This process culminates in a heterogeneous tumor, consisting of multiple subpopulations of cancer cells that often do not contain the same underlying mutations. Continuous selective pressure permits outgrowth of clones that harbor lesions that are capable of enhancing disease progression, including those that contribute to therapy resistance, metastasis and relapse. Clonal evolution and the resulting intratumoral heterogeneity pose a substantial challenge to biomarker identification, personalized cancer therapies and the discovery of underlying driver mutations in cancer. The purpose of this Review is to highlight the unique strengths of zebrafish cancer models in assessing the roles that intratumoral heterogeneity and clonal evolution play in cancer, including transgenesis, imaging technologies, high-throughput cell transplantation approaches and in vivo single-cell functional assays.

KEYWORDS:

Cancer stem cell; Fluorescence; Intratumoral; Single cell; Targeted therapy; Tumor

PMID:
24973745
PMCID:
PMC4073265
DOI:
10.1242/dmm.015842
[Indexed for MEDLINE]
Free PMC Article

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