Abstract SY29-01: Compartmentalization of proteins and drugs in cancer cells

Abstract New insights into condensate compartments in cell biology promise to advance understanding of disease mechanisms and to improve drug discovery and development for cancer. Cells have evolved mechanisms to distribute ∼10 billion protein molecules to condensate compartments where multiple proteins involved in shared functions must assemble. We have found that proteins possess codes both for folding and for selective compartmentalization in biomolecular condensates. Selective protein-protein and protein-nucleic acid interactions are thought to be the predominant driving force leading to the assembly of specific proteins in subcellular compartments, but there is evidence of distinctive chemical environments within condensates, indicating that these compartments have different solvent properties. Thus, patterns of amino acid sequences in proteins both promote specific folding behaviors and favor residence in compartments compatible with their solvent properties. The observation that small molecule drugs, including widely used anti-neoplastic medicines, selectively concentrate in specific condensates has important implications for drug development and therapeutic efficacy. Citation Format: Richard A. Young. Compartmentalization of proteins and drugs in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr SY29-01.