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Review
. 2025 Sep 19:e70122.
doi: 10.1111/cpr.70122. Online ahead of print.

Liquid-Liquid Phase Separation in Major Hallmarks of Cancer

Chen-Chen Xie  1   2   3   4   5 , Ting Wang  1   2   3   4   5 , Xin-Ran Liu  1   2   3   4   5 , Yan Wang  1   2   3   4   5 , Qin Dang  1   2   3   4   5 , Tian Ding  1   2   3   4   5 , Jia-Qi Xu  6 , Xian-Jun Yu  1   2   3   4   5 , Hai Lin  6 , Xiao-Wu Xu  1   2   3   4   5 , Yi Qin  1   2   3   4   5
Affiliations
Review

Liquid-Liquid Phase Separation in Major Hallmarks of Cancer

Chen-Chen Xie et al. Cell Prolif. .

Abstract

The malignant transformation of cancer cells is underpinned by the dysregulation of essential cellular processes, including genome stability maintenance, DNA repair, transcriptional control and signal transduction. These processes are not randomly distributed but are spatiotemporally coordinated through dynamic molecular assemblies. Recent advances have highlighted the pivotal role of biomolecular condensates, membraneless compartments formed via liquid-liquid phase separation (LLPS), in compartmentalising and regulating these key functions. LLPS enables the concentration and organisation of proteins and nucleic acids, creating distinct biochemical environments that facilitate cellular decision-making. Importantly, aberrant phase separation has been increasingly implicated in the acquisition of cancer hallmarks, such as sustained proliferative signalling, resistance to cell death and immune evasion. In this review, we summarise the physicochemical principles of LLPS, examine its emerging roles in oncogenic transformation and discuss the therapeutic potential of targeting phase separation in cancer. Our findings highlight LLPS as a novel and versatile regulatory layer in tumour biology and an emerging frontier in precision oncology.

Keywords: biomolecular condensates; cancer; cancer therapeutics; dysregulated state; liquid–liquid phase separation.

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