Leland Stanford Junior University

Dana-farber-cancer Institute Inc.

Cigall Kadoch

Gerald R Crabtree

William C Hahn

Emily Carla Dykhuizen

Andrew D′Avino

Diana Clare Hargreaves

Nazar Mashtalir

Brittany C Michel

Gabriel Sandoval

The present invention is based, in part, on the novel discovery of the architecture and assembly pathway of three different classes of mammalian SWI/SNF complexes, compositions comprising the isolated modified SWI/SNF complexes, and methods of screening for modulators of the function and/or stability of same.

SWI/SNF family chromatin remodeling complexes and uses thereof

The present invention provides methods of screening for compounds that interfere with the interaction between ERG. ETV1, ETV4 or ETV5 and mSWI/SNF (BAF) chromatin remodeling complex proteins. Included are methods of screening for compounds that interfere with the interaction between ERG, ETV1, ETV4 or ETV5 and BAF155. Methods of treating prostate cancer with compounds that interfere with the interaction between ERG, ETV1, ETV4 or ETV5 and mSWI/SNF (BAF) chromatin remodeling complex proteins are also provided.

Methods of identifying compounds that interfere with ERG-driven misguidance of BAF complexes in TMPRSS2-ERG driven prostate cancers

Methods for identifying and treating cancer patients likely to respond to topoisomerase inhibitors or likely to fail to respond to topoisomerase inhibitors are provided. The methods take advantage of the newly discovered role of BAF complexes in decatenation of DNA by topoisomerase IIa. Cancer cells are frequently at least partly defective in BAF complex activity. Such cells are targeted for therapy using certain topoisomerase IIa inhibitors according to the disclosed methods of treatment. Therapy of such cells using other topoisomerase inhibitors should be avoided.

Methods for identifying and treating cancer patients

Methods and compositions are provided for treating human synovial sarcoma (SS). Also provided are screens to identify therapeutics for the treatment of synovial sarcoma. These methods, compositions, and screens are based on the discovery that promoting the assembly of wild type BAF (also called mSWI/SNF) complexes in SS cells by increasing levels of wild type SS18 and/or decreasing levels of SS18-SSX fusion protein leads to the cessation of proliferation of malignant cells in synovial sarcoma.

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Tiburon, CA, United States of America

Cigall Kadoch