The Johns Hopkins University

Srinivasan Yegnasubramanian

William G Nelson

Xiaohui S Lin

Traci J Speed

Zachery Reichert

Ajay Vaghasia

Philipp Nuhn

William B Isaacs

G Steven Bova

Angelo M DeMarzo

Michael Christoph Haffner

Nicole Anders

Alcides Chaux

Michelle A Rudek-Renaut

Martin Aryee

The disclosure generally relates to compositions and methods for the treatment of cancer. In some aspects, disclosed herein are methods for the induction of synthetic lethality with epigenetic therapy (ISLET) using a combination of at least one epigenetic compound and at least one chemotherapeutic agent. Also disclosed herein are screening methods for identifying compounds that induce killing of cancer cells when combined with at least one epigenetic compound. Further disclosed herein are methods of potentiating a therapeutic effect of a chemotherapeutic agent against a cancer, comprising administering to a subject having the cancer an epigenetic compound in an amount effective to potentiate the therapeutic effect of the chemotherapeutic agent against the cancer.

Induction of synthetic lethality with epigenetic therapy

The present invention provides methods for discovering agents that are effective in reversing epigenetic silencing by inhibiting the interaction of methyl-binding (MBD) proteins with methylated genomic DNA. Also provided are methods for reactivating silenced genes having CpG island hypermethylation along with methods for treatment and prevention of diseases, such as cancer and sickle cell anemia, by administering an agent that modulates methyl-binding domain (MBD) protein-mediated transcriptional repression, thereby increasing gene transcription to prevent or treat disease. Additionally, compounds identified by the present invention useful for treatment and prevention of diseases, such as cancer and sickle cell anemia, are provided.

Agents for reversing epigenetic silencing of genes

This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors.

Quantitative determination of nucleoside analogue drugs in genomic DNA or RNA

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for assessing prostate cancer. In a specific embodiment, present inventors have developed and applied a new technology and associated computation methods enabling simultaneous genome-scale analysis of genetic (copy number) and epigenetic (total methylation (TM) and allele-specific methylation (ASM) alternation, This method, called MBD-SNP, features affinity enrichment or methylated genomic DNA fragments using a methyl-binding domain polypeptide.

DNA methylation markers for metastatic prostate cancer

The present invention relates to the field of cancer. More specifically, the present invention provides methods and compositions useful for diagnosing or predicting cancer in a patient. In one embodiment, a method for identifying a patient as having cancer comprises the steps of (a) providing a formalin-fixed, paraffin-embedded or fresh frozen sample of patient tissue; (b) steaming the sample in antigen retrieval buffer; (c) incubating the sample in hydrochloric acid (HCl); (d) incubating the sample with an affinity reagent specific for 5hmC under conditions to form a complex between the affinity reagent and 5-hydroxymethylcytosine (5hmC) present in the sample; (e) detecting the complexes formed between 5hmC and the affinity reagent with secondary detection reagents; (f) quantifying 5hmC levels; and (g) identifying the patient as having cancer if the 5hmC levels in the sample are reduced as compared to a control.

5-hydroxymethylcytosine in human cancer

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Baltimore, MD, United States of America

Srinivasan Yegnasubramanian