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Cancer Signaling and Epigenetics

Chief Scientific Officer Jonathan Chernoff (left) speaks with James Duncan about the future course of research at Fox Chase. Chief Scientific Officer Jonathan Chernoff (left) speaks with James Duncan about the future course of research at Fox Chase.

The Cancer Signaling and Epigenetics (CSE) Program is focused on making basic scientific discoveries that are relevant to human malignancies. The primary mission of this Program is to determine how a normal cell becomes transformed and develops into a cancer, and how this information can be used to design effective therapies.

Within this purview, members of the CSE Program use biochemical, cell-based, and animal models, as well as patient-derived specimens, to define the impact that the cross-talk within the tumor microenvironment, kinase signaling and epigenetic pathways have on cellular transformation, tumor initiation and progression as well as therapeutic resistance.

The Program focuses on two major themes:

1. Signal Transduction

Cancers arise from mutations in genes that regulate cell proliferation and survival. These mutations activate oncogenic signaling pathways that alter cell survival, proliferation, and motility, and provide targets for rational drug development. Within this theme, members of the CSE Program are examining the hierarchy of communication mechanisms between tumor and stromal cells, and how understanding these signaling circuits can be exploited to develop potential therapeutic targets.

In addition, unique proteomic analytic techniques developed by members of the Program enable the interrogation of drug resistance pathways, a key issue that limits the success of targeted agents in cancer.

2. Epigenetics

Within this theme, CSE members investigate epigenetic mechanisms regulating the DNA (e.g., modifications by methylases and demethylases) and/or chromatin states (e.g., epigenome states and their writers, erasers, and readers) impacting tumorigenesis and therapeutic response with the goal of identifying candidate epigenetic biomarkers that can be used to guide conventional and novel therapeutic strategies.

CSE members also seek to leverage novel epigenetic therapies individually and/or in combination with other therapies in order to more effectively target cancers in our catchment area. Members also seek to build an understanding about how signaling networks impinge on epigenetic programs, and in turn, control drug response.

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