1. Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
2. Chengdu University of Traditional Chinese Medicine, Chengdu 610041, Sichuan, China.
3. Shanghai ETERN Biopharma Co., Ltd., Shanghai, China.
4. School of Pharmacy, Chengdu Medical College, Xindu Avenue No 783, Chengdu, 610500, Sichuan Province, China.
5. West China School of Nursing, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
* Zheran Liu, Zijian Qin and Yingtong Liu contributed equally to this work.
Liquid‒liquid phase separation (LLPS) is a phenomenon driven by weak interactions between biomolecules, such as proteins and nucleic acids, that leads to the formation of distinct liquid-like condensates. Through LLPS, membraneless condensates are formed, selectively concentrating specific proteins while excluding other molecules to maintain normal cellular functions. Emerging evidence shows that cancer-related mutations cause aberrant condensate assembly, resulting in disrupted signal transduction, impaired DNA repair, and abnormal chromatin organization and eventually contributing to tumorigenesis. The objective of this review is to summarize recent advancements in understanding the potential implications of LLPS in the contexts of cancer progression and therapeutic interventions. By interfering with LLPS, it may be possible to restore normal cellular processes and inhibit tumor progression. The underlying mechanisms and potential drug targets associated with LLPS in cancer are discussed, shedding light on promising opportunities for novel therapeutic interventions.
Keywords: liquid‒liquid phase separation, biomolecular condensates, hematologic neoplasms, solid tumors