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Mechanisms and clinical implications of tumor heterogeneity and convergence on recurrent phenotypes

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Abstract

Tumor heterogeneity has been identified at various -omic levels. The tumor genome, transcriptome, proteome, and phenome can vary widely across cells in patient tumors and are influenced by tumor cell interactions with heterogeneous physical conditions and cellular components of the tumor microenvironment. Here, we explore the concept that while variation exists at multiple -omic levels, changes at each of these levels converge on the same pathways and lead to convergent phenotypes in tumors that can provide common drug targets. These phenotypes include cellular growth and proliferation, sustained oncogenic signaling, and immune avoidance, among others. Tumor heterogeneity complicates treatment of patient cancers as it leads to varied response to therapies. Identification of convergent cellular phenotypes arising in patient cancers and targeted therapies that reverse them has the potential to transform the way clinicians treat these cancers and to improve patient outcome.

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Acknowledgements

The authors wish to thank Dr. Samuel W. Brady for manuscript editing.

Funding information

This work was supported by funding from the National Institutes of Health (U54CA209978).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA

    Jasmine A. McQuerry & Andrea H. Bild

  2. Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA

    Jasmine A. McQuerry

  3. Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX, USA

    Jeffrey T. Chang

  4. Peter MacCallum Cancer Centre, Parkville, VIC, Australia

    David D. L. Bowtell

  5. Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, VIC, Australia

    David D. L. Bowtell

  6. Kinghorn Cancer Centre, Garvan Institute for Medical Research, Darlinghurst, Sydney, NSW, Australia

    David D. L. Bowtell

  7. Oncology Division, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Adam Cohen

  8. Department of Medical Oncology and Therapeutics, City of Hope, Duarte, CA, USA

    Andrea H. Bild

Authors
  1. Jasmine A. McQuerry
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  2. Jeffrey T. Chang
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  3. David D. L. Bowtell
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  4. Adam Cohen
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  5. Andrea H. Bild
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Correspondence to Andrea H. Bild.

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McQuerry, J.A., Chang, J.T., Bowtell, D.D.L. et al. Mechanisms and clinical implications of tumor heterogeneity and convergence on recurrent phenotypes. J Mol Med 95, 1167–1178 (2017). https://doi.org/10.1007/s00109-017-1587-4

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  • DOI: https://doi.org/10.1007/s00109-017-1587-4

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