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Journal of Molecular Medicine

, Volume 95, Issue 11, pp 1167–1178 | Cite as

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

  • Jasmine A. McQuerry
  • Jeffrey T. Chang
  • David D. L. Bowtell
  • Adam Cohen
  • Andrea H. Bild
Review

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.

Keywords

Tumor heterogeneity Convergent phenotypes Tumor microenvironment Cancer therapy 

Notes

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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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Jasmine A. McQuerry
    • 1
    • 2
  • Jeffrey T. Chang
    • 3
  • David D. L. Bowtell
    • 4
    • 5
    • 6
  • Adam Cohen
    • 7
  • Andrea H. Bild
    • 1
    • 8
  1. 1.Department of Pharmacology and ToxicologyUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Oncological SciencesUniversity of UtahSalt Lake CityUSA
  3. 3.Department of Integrative Biology and PharmacologyUniversity of Texas Health Science Center at HoustonHoustonUSA
  4. 4.Peter MacCallum Cancer CentreParkvilleAustralia
  5. 5.Sir Peter MacCallum Cancer Centre Department of OncologyUniversity of MelbourneParkvilleAustralia
  6. 6.Kinghorn Cancer CentreGarvan Institute for Medical ResearchSydneyAustralia
  7. 7.Oncology Division, Department of Internal Medicine, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  8. 8.Department of Medical Oncology and TherapeuticsCity of HopeDuarteUSA

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