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Cancer cells exhibit clonal diversity in phenotypic plasticity
Robert Austin Mathis1,2, Ethan S Sokol1,2, Piyush B Gupta3,2,4,5
1Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.
Open Biology
|February 17, 2017
Summary
Cancer cells can switch between states, impacting treatment. This study shows that alternating therapies can select for more adaptable cancer cells, but faster alternation may minimize this effect.
Area of Science:
- Cancer biology
- Cellular plasticity
- Genomics
Background:
- Phenotypic heterogeneity in cancer drives progression and drug resistance.
- Cancer cell plasticity, the ability to switch states, is crucial but poorly understood.
- Epithelial and mesenchymal phenotypes are key states in cancer progression.
Purpose of the Study:
- To quantify and track phenotypic plasticity in cancer cell populations.
- To evaluate the impact of combination therapies on phenotypic heterogeneity.
- To identify strategies for optimizing combination therapy efficacy.
Main Methods:
- Utilized DNA barcoding to track phenotypic states across hundreds of cancer cell clones.
- Quantified the epithelial-to-mesenchymal cell ratio and its heritability.
- Developed quantitative simulations based on experimental barcoding data.
Main Results:
- Found significant variability in epithelial-to-mesenchymal cell ratios across clones, but stability within clonal lineages (heritability of 0.89).
- Simulations revealed that alternating therapies select for increased cancer cell plasticity.
- Increasing the frequency of treatment alternation can minimize this selection pressure.
Conclusions:
- Phenotypic plasticity is a heritable trait in cancer cells.
- Current alternating combination therapies may inadvertently promote cancer cell adaptability.
- Optimized treatment alternation frequency is key to effective cancer therapy design.
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