Tumor heterogeneity: causes and consequences

By A. Marusyk, K. Polyak. Biochimica et Biophysica Acta, 2009

1,616 citations recorded by the source corpus.

With rare exceptions, spontaneous tumors originate from a single cell. Yet, at the time of clinical diagnosis, the majority of human tumors display startling heterogeneity in many morphological and physiological features, such as expression of cell surface receptors, proliferative and angiogenic potential. To a substantial extent, this heterogeneity might be attributed to morphological and epigenetic plasticity, but there is also strong evidence for the co-existence of genetically divergent tumor cell clones within tumors. In this perspective, we summarize the sources of intra-tumor phenotypic heterogeneity with emphasis on genetic heterogeneity. We review experimental evidence for the existence of both intra-tumor clonal heterogeneity as well as frequent evolutionary divergence between primary tumors and metastatic outgrowths. Furthermore, we discuss potential biological and clinical implications of intra-tumor clonal heterogeneity.

Subfields: Cancer Research, Cell Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/156f63561a2ad137ef2cf4f29fdd55c6a08355bf

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Citations in the corpus

Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor (2012, background): “Both clonal evolution and cancer stem cell models suggest that drug resistance and tumor relapse are the result of intratumoral heterogeneity and subpopulation diversity of cancer cells (Marusyk and Polyak, 2010; Visvader, 2011).”
CLONAL EVOLUTION IN CANCER (2012, background): “Subclonal genetic heterogeneity is a common, if not universal, feature of cancer”
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics (2013, background): “Instead of benefitting single clones, this would favor the whole tumor population by converting heterogeneity into an asset to resist treatment (7, 42).”
Immune evasion in cancer: Mechanistic basis and therapeutic strategies. (2015, background): “[68] Marusky A, Polyak K.”
Systematic Analysis of Breast Cancer Morphology Uncovers Stromal Features Associated with Survival (2011, background): “This degree of intrapatient agreement is only moderate, and these findings suggest significant intrapatient tumor heterogeneity, which is a cardinal feature of breast carcinomas ( 33 – 35 ).”
Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). (2012, background): “Cancer cells may change their metabolic phenotypes to adapt to microenvironmental changes and the results of these changes give a selective advantage to cancer cells under the unfavorable environment (14,15).”
BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. (2010, background): “Rather, the profiles suggested that clonal selection was occurring, possibly within a pool of cancer stem cell-like cells (Marusyk and Polyak, 2010).”
Nanoparticles in the clinic (2016, background): “The complexities associated with species-barrier issues are further complicated when considering the heterogeneity of human disease.(122,123) Fortunately, efforts to correlate human and small animal data are increasing given the increasing number of clinical trials.”
Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. (2011, background): “Tumor heterogeneity is defined by the presence of cell subpopulations harboring distinct genetic or gene expression profiles with distinct biologic properties (Marusyk and Polyak, 2010) and plays a crucial role in tumor progression and resistance to therapy (Gerlinger and Swanton, 2010).”