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Perspective ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00842

A model-system to address the impact of phenotypic heterogeneity and plasticity in the development of cancer therapies

  • 1University of Toronto, Canada
  • 2Canadian College of Naturopathic Medicine, Canada
  • 3University of New Brunswick Fredericton, Canada

The main challenges in developing effective anti-cancer therapies stem from the highly complex and heterogeneous nature of cancer, including the presence of multiple genetically-encoded and environmentally-induced cancer cell phenotypes within an individual. This diversity can make the development of successful treatments difficult as different phenotypes can have different responses to the same treatment. The lack of model-systems that can be used to simultaneously test the effect of therapies on multiple distinct phenotypic states further contributes to this problem. To mitigate these challenges, we suggest that in vitro model-systems that consist of several genetically-related but phenotypically distinct populations can be used as proxies for the several phenotypes present in a patient with advanced disease. As proof of concept, we have developed such a model and showed that different phenotypes had different responses to the same challenge both in terms of sensitivity and phenotypic plasticity. We suggest that similar model-systems could be developed and used when designing novel therapeutic strategies, to address the potential impact of phenotypic heterogeneity and plasticity of cancer on the development of successful therapies. Specifically, the effect of a therapy should be considered on more than one cancer cell phenotype, and both cell viability and changes in phenotypic state (to address potential plastic responses) should be evaluated. Although we are aware of the limitations of in vitro systems, we believe that the use of established cell lines that express multiple phenotypes can provide invaluable insights into the complex interplay between therapies and cancer’s heterogeneous and plastic nature.

Keywords: extracellular pH, phenotypic plasticity, therapy, H2122, metastasis, experimental evolution, selection, microenvironment

Received: 20 Feb 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Jong, Chan and Nedelcu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Aurora M. Nedelcu, University of New Brunswick Fredericton, Fredericton, Canada,