Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.

Biomolecular condensates formed through liquid-liquid phase separation (LLPS) have emerged as central organizers of cellular biochemistry. In cancer, dysregulated phase separation gives rise to oncogenic condensates that reprogram transcriptional, signaling, and stress-response networks. By selectively concentrating oncogenic proteins and nucleic acids, these dynamic assemblies create permissive regulatory microenvironments that stabilize malignant cell states and facilitate therapeutic resistance. Accumulating evidence now indicates that oncogenic condensates are pharmacologically tractable, opening new opportunities for targeted intervention. In this Review, we synthesize current mechanistic insights into condensate assembly, regulation, and material state transitions; examine their context-dependent behaviors and functional heterogeneity across tumor ecosystems; and delineate emerging therapeutic strategies, including small-molecule modulators, peptide-based inhibitors, targeted protein degraders, and RNA-directed approaches. We further highlight recent translational advances-exemplified by DPTX-3186, a first-in-class condensate modulator granted FDA Orphan Drug Designation for Wnt-driven gastric cancer-that underscore the clinical promise of condensate-directed therapies. Finally, we discuss key mechanistic, pharmacodynamic, and biomarker-related challenges that must be addressed to fully integrate condensate biology into next-generation precision oncology.