Dana-farber-cancer Institute Inc.

Johns Hopkins University

Other

The General Hospital Corporation

Kornelia Polyak

Dale Porter

Bert Vogelstein

Kenneth W Kinzler

Ian Krop

James Elliott Bradner

James Bradner

Dennis Sgroi

Jun Yao

Charlotta Enerbäck

Min Hu

Noga Qimron

Vanessa Almendro

Sibgat Choudhury

Shaokun Shu

Charles Yang Lin

The present disclosure provides combination therapy comprising a BET inhibitor and a protein phosphatase 2A (PP2A) activator, a B-cell lymphoma-2 (Bcl-2) inhibitor, a B-cell lymphoma-extra large (Bcl-xl) inhibitor, a casein kinase 2 (CK2) inhibitor, and/or a mediator complex subunit 1 (MED1) for cancer. The combination therapy is expected to be synergistic in treating the cancer, compared to the monotherapy. Methods for identifying a subject having a cancer that is resistant to or at risk of developing resistance to bromodomain and extra terminal (BET) inhibitor therapy are also provided.

Mechanism of resistance to bet bromodomain inhibitors

Methods for treating, preventing and predicting a subject's risk of developing breast cancer are provided.

Methods for treating, preventing and predicting risk of developing breast cancer

The invention provides a method of analyzing the methylation status of all or part of an entire genome. Moreover, the invention features methods of and reagents for characterizing biological cells containing DNA that is susceptible to methylation. Such methods include methods of diagnosing cancer, e.g., breast cancer.

Gene methylation and expression

This invention encompasses antibodies specific for IBC-1 (Invasive Breast Cancer-1), methods for diagnosis and prognosis of metastatic breast cancer and degenerative neural conditions, methods of identifying and manufacturing therapeutic compounds, and methods of treating patients with invasive and metastatic breast cancer or degenerative neural conditions.

IBC-1 (Invasive Breast Cancer-1), a putative oncogene amplified in breast cancer

The invention encompasses isolated DNAs encoding HIN-1 polypeptides, vectors containing such DNAs, cells containing the vectors, and isolated HIN-1 polypeptides. The invention also features methods of making and using HIN-1 polypeptides.

HIN-1, a tumor suppressor gene

The invention features methods of diagnosing high grade ductal carcinoma in situ (DCIS) These methods involve measuring: (1) the level of HID-5 in a body fluid (e.g., blood or urine) of a subject suspected of having, or at risk of having, high grade DCIS; or (2) the level of HID-5 gene expression in breast tissue from a subject suspected of having, or at risk of having, high grade DCIS. The invention also embodies a method of inhibiting expression of HID-5 protein in DCIS cells and methods of treating a subject suspected of having, or at risk of having, high grade DCIS.

Psoriasin expression by breast epithelial cells

IBC-1 (invasive breast cancer-1), a putative oncogene amplified in breast cancer

The accumulation of homoplasmic somatic mutations has been observed in the mitochondrial DNA of certain tumor cells. The presence or recurrence of a tumor can be detected by determining the presence of single basepair mutations in the mitochondrial genome from a cell sample of a patient.

Subtle mitochondrial mutations as tumor markers

The most well-documented biochemical property of p53 is its ability to transcriptionally activate genes. Many of the genes which are activated by p53 expression prior to the onset of apoptosis are predicted to encode proteins which could generate or respond to oxidative stress, including one that is implicated in apoptosis within plant meristems. p53 may result in apoptosis through a three-step process: (I) the transcriptional induction of specific redox-related genes; (ii) the formation of reactive oxygen species (ROS); and (iii) the oxidative degradation of mitochondrial components, rapidly leading to cell death. Transcription of other genes is decreased by p53. Examination of the level of transcription of p53-induced or repressed genes can be used to determine p53 status, to diagnose cancer, and to evaluate cytotoxicity or carcinogenicity of a test agent.

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Brookline, MA, United States of America

Kornelia Polyak