Oncogenic kinase fusions are among the most frequent and therapeutically actionable drivers of human cancers, yet their mechanistic diversity remains underappreciated. By systematically characterizing dozens of kinase alterations, we uncovered a unifying principle: most fusion kinases assemble into biomolecular condensates that serve as organizing centers for aberrant signaling. The kinase domain largely determines which signaling pathways are engaged, such as MAPK or PI3K, while the fusion partner defines subcellular localization and the cohort of recruited effectors. In-depth analyses of EML4–ALK variants, a hallmark of lung adenocarcinoma, reveal that distinct EML4 segments produce condensates with unique proteomic compositions and variable responses to ALK inhibitors. Core signaling adaptor proteins co-localize with and are required for condensate formation, linking condensate assembly directly to oncogenic signaling output. Together, these findings show that fusion architecture encodes a structural “logic” for signal rewiring and drug response, underscoring how understanding condensate biology can refine our strategies for precision targeting of kinase-driven cancers.

Anne-Claude Gingras is the Vice President of Research at Sinai Health and Director of the Lunenfeld-Tanenbaum Research Institute in Toronto. She holds the Canada Research Chair in Functional Proteomics and the inaugural Lou Siminovitch Chair. A Full Professor in the Department of Molecular Genetics at the University of Toronto, she is the co-director of the Network Biology Collaborative Centre at the Lunenfeld-Tanenbaum Research Institute, where she is also a Senior Investigator. Her laboratory studies signalling pathways and dynamic cellular organization in health and disease using systematic approaches and developing quantitative proteomics technologies.

She has developed computational tools that enable better analysis and visualization of proteomics results, and she contributes to training the next generation of proteomics researchers. Using the tools she developed, her group has identified new protein complexes and signalling components that better understand perturbations associated with cancer and rare diseases.

She also contributed to Canada’s response to the COVID-19 pandemic by developing high-throughput and functional serology assays. Dr. Gingras has published >300 research articles and review articles already cited >67,000 times. She has been recognized through election to the Royal Society of Canada (2015) and the European Molecular Biology Organization (EMBO, 2020), in addition to being awarded for her proteomics discoveries (Molecular and Cellular Proteomics Lectureship Award, 2018; Human Proteome Organization, HUPO, Discovery in Proteomics Science Award, 2019; Canadian National Proteomics Network Tony Pawson Award, 2020) and multiple named lectures.