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A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC.

Cancer cell | Jul 13, 2015

Epigenetic dysregulation has emerged as an important mechanism in cancer. Alterations in epigenetic machinery have become a major focus for targeted therapies. The current report describes the discovery and biological activity of a cyclopropylamine containing inhibitor of Lysine Demethylase 1 (LSD1), GSK2879552. This small molecule is a potent, selective, orally bioavailable, mechanism-based irreversible inactivator of LSD1. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) is sensitive to LSD1 inhibition. The subset of SCLC lines and primary samples that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes, suggesting this may be used as a predictive biomarker of activity.

Pubmed ID: 26175415 RIS Download

Mesh terms: Administration, Oral | Animals | Antineoplastic Agents | Benzoates | Cell Line, Tumor | Cell Proliferation | Cyclopropanes | DNA Methylation | Enzyme Inhibitors | Epigenesis, Genetic | Gene Expression Regulation, Neoplastic | Histone Demethylases | Humans | Lung Neoplasms | Mice | Molecular Sequence Data | Small Cell Lung Carcinoma | Xenograft Model Antitumor Assays

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Human Biological Data Interchange

Database of medical history and genealogical data on over 6700 families who are affected by type 1 diabetes and a repository of DNA and immortalized cell lines collected from 500 families. This database and repository was originally created to help researchers uncover the genetic causes of type 1 diabetes but today, it is also used by researchers who study type 2 diabetes, diabetic complications, autoimmune diseases, kidney disease, and other disorders. The following resources and services are available to researchers through HBDI: * International Type 1 Diabetes Database: This database includes more than 6700 families with diabetes, related complications and other genetic diseases. There are extensive genealogical and medical histories for more than 90,000 individuals. NDRI conducts searches of the database for approved research requests. * HBDI Catalog: The catalog contains 503 family pedigrees with associated cell lines, DNA, and serum for research. Also available are HLA-typing and auto-antibody test results for diabetes families in the catalog. * HBDI Repository: The HBDI repository contains cell lines, DNA, and HLA typing information from 480 families, and frozen buffy coats from 23 families, all with Type 1 diabetes. They have recently expanded the repository to include specimens from individuals with rare diseases. * Customized Collections: NDRI will collect data from patients and physicians, conduct phone interviews and collect blood and other specimens for research on request.

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