# Hallmark (2022): unlocking phenotypic plasticity

Source: https://onco.cc/terms/unlocking-phenotypic-plasticity/  
OnCo record `unlocking-phenotypic-plasticity` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cancer cells escape the normal rule that mature cells stay what they are: they dedifferentiate, transdifferentiate, or refuse to mature.

## Summary

Unlocking phenotypic plasticity, a hallmark added in 2022, describes how cancer cells escape the rule that mature cells stay what they are: they dedifferentiate, transdifferentiate or refuse to mature. Examples are lineage plasticity under therapy (neuroendocrine transformation in prostate and lung cancer), dedifferentiation in melanoma and thyroid cancer and blocked differentiation in leukaemia, covered in the Histologic transformation entry. The responses are differentiation therapy (ATRA, menin inhibitors) and plasticity-blocking epigenetic drugs, which is why Menin, EZH2 and DLL3 are the linked targets. Readers reach it from the Hallmarks of Cancer overview, the 2022 hallmarks paper and the Lineage plasticity & neuroendocrine transformation pathway.

## Fields

- Kind: Term
- Last checked: 2026-09-08
- Tags: hallmark

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer
- Hanahan, Hallmarks of Cancer: New Dimensions (Cancer Discovery 2022): https://doi.org/10.1158/2159-8290.CD-21-1059

## Connected records

- targets: [DLL3](https://onco.cc/targets/dll3/), [EZH2](https://onco.cc/targets/ezh2/), [Menin](https://onco.cc/targets/menin/)
- pathways: [Cancer stem cells & phenotypic plasticity](https://onco.cc/pathways/cancer-stem-cells-plasticity/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/)
- terms: [Cancer stem cell theory and phenotypic plasticity](https://onco.cc/terms/cancer-stem-cell-theory/), [Hallmarks of Cancer](https://onco.cc/terms/hallmarks-of-cancer/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/), [Histologic transformation](https://onco.cc/terms/histologic-transformation/)
- key papers: [Hallmarks of Cancer 2022: adding phenotypic plasticity, epigenetic reprogramming, microbiomes and senescent cells](https://onco.cc/key-papers/paper-hallmarks-new-dimensions-cancer-discov-2022/)

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