FUNDED INVESTIGATORS

 

From left: Robert A. Casero, Ph.D., Cynthia Zahnow, Ph.D., Stephen Baylin, M.D.
Johns Hopkins University

COMBINING THE POWER OF EPIGENETICS AND IMMUNOTHERAPY TO DEVELOP NEW CANCER THERAPIES.

The Goal

The overall goal of the studies in this collaborative effort is to exploit the fact that epigenetic changes are reversible by developing therapies that restore the expression of aberrantly silenced genes, thus restoring growth control to tumors.

About the Researchers

Dr. Casero is a molecular pharmacologist whose laboratory aided in the discovery of the first documented lysine-specific demethylase, LSD1, a histone-modifying enzyme that is capable of broadly and aberrantly Silencing gene expression.

Dr. Zahnow's expertise is in breast cancer and in understanding how aberrant epigenetic silencing interacts with, and disrupts normal cellular signaling and leads to tumorigenesis. Dr. Zahnow's project will focus on the combination of epigenetically targeted agents in combination with standard chemotherapeutic agents to optimize such a strategy for clinical use.

Dr. Baylin is an expert in cancer epigenetics and helped develop and refine the concepts of how promoter DNA methylation, in concert with chromatin modification, act in concert to initiate and maintain silencing of genes.

Methodology

Cancers are the result of genetic and epigenetic changes resulting in tumors that have lost normal growth control. Genetic changes are those resulting from mutation, loss, change in copy number, and rearrangement of genes. Epigenetic changes refer to changes in chromatin that are not a result in DNA sequence changes but are represented by DNA base modification, such as DNA methylation, and modifications of histone proteins. In cancer, epigenetic silencing of important growth control genes, called tumor suppressor genes, frequently contributes to the initiation and progression of cancer.

Clinical Implications

This SWCRF-funded team has produced work that is the basis for current clinical trials that are exploiting the fact that specific epigenetic treatments lead to increased tumor sensitivity to immune therapy.

Read about recent findings in Dr. Zahnow's research with implications for ovarian cancer treatment.

Dr. Baylin's work in epigenetics has launched a trial for a potential lung cancer drug.