The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity

Alastair Davies, Amina Zoubeidi, Himisha Beltran, Luke A. Selth

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Lineage plasticity, a process whereby cells change their phenotype to take on a different molecular and/or histologic identity, is a key driver of cancer progression and therapy resistance. Although underlying genetic changes within the tumor can enhance lineage plasticity, it is predominantly a dynamic process controlled by transcriptional and epigenetic dysregulation. This review explores the transcriptional and epigenetic regulators of lineage plasticity and their interplay with other features of malignancy, such as dysregulated metabolism, the tumor microenvironment, and immune evasion. We also discuss strategies for the detection and treatment of highly plastic tumors. SIGNIFICANCE: Lineage plasticity is a hallmark of cancer and a critical facilitator of other oncogenic features such as metastasis, therapy resistance, dysregulated metabolism, and immune evasion. It is essential that the molecular mechanisms of lineage plasticity are elucidated to enable the development of strategies to effectively target this phenomenon. In this review, we describe key transcriptional and epigenetic regulators of cancer cell plasticity, in the process highlighting therapeutic approaches that may be harnessed for patient benefit.
Original languageEnglish
Pages (from-to)1771-1788
Number of pages18
JournalCancer Discovery
Issue number8
Early online date20 Jul 2023
Publication statusPublished - 1 Aug 2023


  • Cancer cells
  • Plasticity
  • Lineage Plasticity


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