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Gramling S, Reisman D. Discovery of BRM Targeted Therapies: Novel Reactivation of an Anti-cancer Gene. Lett Drug Des Discov. 2011;8(1):93-99doi: 10.2174/157018011793663840.
Gramling, S., & Reisman, D. (2011). Discovery of BRM Targeted Therapies: Novel Reactivation of an Anti-cancer Gene. Letters in drug design & discovery, 8(1), 93-99. https://doi.org/10.2174/157018011793663840
Gramling, Sarah, and Reisman, David. "Discovery of BRM Targeted Therapies: Novel Reactivation of an Anti-cancer Gene." Letters in drug design & discovery vol. 8,1 (2011): 93-99. doi: https://doi.org/10.2174/157018011793663840
Gramling S, Reisman D. Discovery of BRM Targeted Therapies: Novel Reactivation of an Anti-cancer Gene. Lett Drug Des Discov. 2011 Jan 01;8(1):93-99. doi: 10.2174/157018011793663840. PMID: 23565070; PMCID: PMC3615482.
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Lett Drug Des Discov. 2011 Jan 01;8(1):93-99. doi: 10.2174/157018011793663840.

Discovery of BRM Targeted Therapies: Novel Reactivation of an Anti-cancer Gene.

Letters in drug design & discovery

Sarah Gramling, David Reisman

Affiliations

  1. Department of Medicine, Division of Hematology/Oncology, University of Florida, Gainesville Florida 32611, USA.

PMID: 23565070 PMCID: PMC3615482 DOI: 10.2174/157018011793663840

Abstract

Drug discovery in the field of oncology has been advanced mainly through the targeting of receptor tyrosine kinases. Both antibodies and small molecule inhibitors have been found to have successful applications in blocking the proliferative functions of these cell surface receptors. Based on these early successes, additional kinases within the cytoplasm have been found to promote cancer and, as such, have been recognized as feasible targets for additional modes of therapies. Unlike these oncogene targets, most tumor suppressors are irreversibly altered during cancer progression and therefore are not feasible targets for therapy. However, a subset of these genes is reversibly epigenetically suppressed. One such gene is BRM, and when it is re-expressed in cancer cells, this gene halts their growth. Moreover, as the key catalytic subunit of the SWI/SNF complex, BRM is centrally important to a host of anticancer pathways and cellular mechanisms, and its status may serve as a biomarker. Restoring its expression will both reconnect a number of growth-controlling pathways and affect cellular adhesion, DNA repair, and immune functions. For these reasons, restoring BRM expression is not only feasible, but potentially a potent form of anticancer therapy. To identify BRM-restoring compounds, we developed a cell-based luciferase assay. In this review, we discuss some of the challenges we encountered, issues related to this type of drug discovery, and our future ambitions. We hope this review will provide insight to this type of endeavor and lead to more investigations pursuing this type of drug research.

Keywords: Anticancer; Brahma; Epigenetic suppression; High throughput screening; SWI/SNF; Tumor suppressor

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