<p>Abnormal phase separation, especially liquid-liquid phase separation (LLPS), drives disease progression by assembling membraneless organelles and biomolecular condensates and further perturbing key cellular processes. LLPS has garnered increasing attention for its application prospects in cancer treatment. A series of strategies, including the modulation of protein concentration, the regulation of post-translational modifications (PTMs), and the development of small molecules that directly interact with biomolecular condensates, hold significant promise for novel anticancer therapies. This review summarizes the newly discovered roles and mechanisms of dysregulated LLPS in different types of cancer, focusing on transcriptional condensates, signaling and stress condensates, DNA damage response, and oncogenic fusion proteins. Epigenetic mechanisms underlying LLPS dysregulation in cancer, and fresh findings in LLPS-based anticancer strategies are also reviewed. In summary, unraveling the oncogenic roles, therapeutic potentials, and epigenetic regulatory mechanisms of liquid-liquid phase separation will help develop novel strategies for cancer control and for overcoming drug resistance.</p>

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Liquid-liquid phase separation in cancer: oncogenic roles, therapeutic potential, and epigenetic regulation

  • Zi-Hui Zhao,
  • Tao Li,
  • Zhi-Zhou Shi

摘要

Abnormal phase separation, especially liquid-liquid phase separation (LLPS), drives disease progression by assembling membraneless organelles and biomolecular condensates and further perturbing key cellular processes. LLPS has garnered increasing attention for its application prospects in cancer treatment. A series of strategies, including the modulation of protein concentration, the regulation of post-translational modifications (PTMs), and the development of small molecules that directly interact with biomolecular condensates, hold significant promise for novel anticancer therapies. This review summarizes the newly discovered roles and mechanisms of dysregulated LLPS in different types of cancer, focusing on transcriptional condensates, signaling and stress condensates, DNA damage response, and oncogenic fusion proteins. Epigenetic mechanisms underlying LLPS dysregulation in cancer, and fresh findings in LLPS-based anticancer strategies are also reviewed. In summary, unraveling the oncogenic roles, therapeutic potentials, and epigenetic regulatory mechanisms of liquid-liquid phase separation will help develop novel strategies for cancer control and for overcoming drug resistance.