Liquid–liquid phase separation in cancer: mechanisms, biological functions, and therapeutic perspectives

Liquid–liquid phase separation (LLPS) is a biophysical process through which biomolecules demix into coexisting dense and dilute liquid phases, whereas biomolecular condensation encompasses a broader range of mechanisms and material states. Aberrant condensate behavior is increasingly implicated in cancer, but many intracellular assemblies attributed to LLPS have not been validated using rigorous experimental criteria. This review therefore provides an evidence-oriented framework for understanding LLPS and biomolecular condensates in cancer. We first clarify their definitions and the experimental criteria used to distinguish LLPS from alternative forms of biomolecular assembly. We then examine the molecular determinants and regulatory factors that govern condensate formation, composition, dynamics, and material properties. Next, we discuss how cancer-associated mutations, fusion proteins, altered post-translational modifications, and changes in the cellular environment reshape condensate behavior. Their functional consequences are critically evaluated across signaling and transcription, genome maintenance, metastasis and cellular plasticity, tumor immunity, and therapeutic resistance, with emphasis on shared mechanistic principles. Finally, we assess emerging condensate-directed therapeutic strategies according to the strength of their experimental and clinical evidence and discuss the major challenges facing their translation. By distinguishing established LLPS mechanisms from broader or incompletely characterized condensation phenomena, this review provides a rigorous conceptual framework for interpreting condensate biology and evaluating its predominantly preclinical therapeutic potential in cancer.