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Updated: Aug 5, 2026
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Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation
Published on: September 19, 2019
Developmentally constrained plasticity as a therapeutic vulnerability in cancer
Jie-Shen Xian1, Yuan-Xiang Yang2, Wei-Ling Li3
1The First Clinical School of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 511436, China.
Neoplasia (New York, N.Y.)
|July 29, 2026
Summary
Cancer cells exhibit plasticity, adapting to therapy by changing states. Understanding these resistance modes—lineage-maintained, adaptive reversible, or fixed reprogramming—guides targeted cancer treatments.
Area of Science:
- Oncology
- Developmental Biology
- Cancer Cell Biology
Background:
- Cancer cells adapt to therapy by altering their phenotype, a process known as malignant plasticity.
- This heterogeneity can involve reversible persister states or stable alternative lineage programs.
- Factors like cell of origin, lineage history, and tumor microenvironment constrain these adaptive transitions.
Purpose of the Study:
- To frame malignant plasticity as developmentally constrained rather than limitless.
- To classify cancer resistance into distinct modes based on lineage and plasticity.
- To guide therapeutic strategies based on identified resistance modes.
Main Methods:
- Conceptual framework integrating developmental biology principles with cancer resistance.
- Classification of resistance into three modes: lineage-maintained, adaptive reversible plasticity, and fixed reprogramming.
- Discussion of multi-omics and perturbational studies for mapping plasticity.
Main Results:
- Malignant plasticity is constrained by intrinsic cellular and extrinsic ecosystem factors.
- Three distinct modes of therapeutic resistance are identified: lineage-maintained, adaptive reversible, and fixed reprogramming.
- Therapeutic strategies should be tailored to the specific resistance mode.
Conclusions:
- A resistance-mode-guided approach refines therapeutic hypotheses for cancer treatment.
- Understanding plasticity and its constraints is crucial for overcoming therapeutic resistance.
- Future research should leverage multi-omics and functional studies to map and target cancer plasticity.
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