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Cancer pathogenesis and phase targeting through condensate fragility
Menghua Wang1, Takudzwa Chiwoneso2, Zimeng Luo2
1State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Department of Chemistry, The University of British Columbia, Vancouver, BC V6T 1Z1, Canada.
Trends in Pharmacological Sciences
|March 7, 2026
Summary
Nuclear liquid-liquid phase separation (LLPS) organizes cell functions. Aberrant LLPS in cancer creates fragile condensates, offering a new therapeutic target by exploiting their instability.
Area of Science:
- Molecular Biology
- Biophysics
- Cancer Research
Background:
- Nuclear liquid-liquid phase separation (LLPS) organizes transcription and DNA repair into dynamic condensates, crucial for genome integrity.
- Dysregulated LLPS is a key driver of oncogenesis, but its role in promoting both transcriptional addiction and genomic instability is not fully understood.
Purpose of the Study:
- To review the role of aberrant nuclear LLPS in cancer pathogenesis and therapy resistance.
- To propose phase targeting through condensate fragility as a precision oncology strategy.
Main Methods:
- Review of recent biophysical and molecular advances in LLPS.
- Analysis of how cancer-associated mutations affect condensate properties.
- Integration of oncogenic mechanisms with biophysical vulnerabilities.
Main Results:
- Cancer-associated mutations rewire LLPS to form hyperstable yet fragile condensates.
- Aberrant nuclear LLPS contributes to both transcriptional addiction and genomic instability in cancer.
Conclusions:
- Targeting the fragility of aberrant nuclear condensates presents a novel precision oncology strategy.
- This approach integrates oncogenic mechanisms with actionable biophysical vulnerabilities for cancer therapy.
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