University of Pittsburgh Cancer Institute (UPCI)

Hormones and Signal Transduction

The tumor environment places enormous stress on cancer cells. MCCBP members are involved in studies of cellular responses to stress, gene expression, and signal transduction in normal and tumor cells. Signal transduction and subsequent changes in gene expression within cells is a primary control for growth and differentiation, and its dysfunction in cancer cells is of particular interest to many program members.

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Selected Publications

• The MYC oncogenic transcription factor is overexpressed in most human cases of T cell acute lymphoblastic leukemia (T-ALL). Genetic alterations in the PTEN-PI3K-AKT pathway are also common in T-ALL. New findings indicate that Akt pathway activation is sufficient for tumor maintenance in a zebrafish model, even after loss of survival signals driven by the MYC oncogene (Gutierrez A, et. al., J Exp Med 208:1595-603, 2011).
• Searching for new drug targets is essential for the development of novel treatment paradigms in cancer. New tools are needed to develop innovative and diverse scaffolds for synthetic roots to new "chemical space." Mutations in p53 account for about 50% of tumors, and inhibition of ATM and ATR, two proteins involved in cell cycle control in p53-deficient cells, can cause synthetic lethality. New synthetic routes were used to develop a new class of such inhibitors. Cancer cells often have higher levels of stress response proteins such as heat shock proteins. A new library of compounds was created by novel synthetic approaches to inhibit heat shock protein 70 which displayed a wide array of pharmacological parameters (Huryn DM Proc Natl Acad Sci U S A. 2011 Apr 26;108:6757-62).
• Resveratrol, trans-3, 4', 5,-trihydroxystilbene, suppresses multiple myeloma (MM), and the endoplasmic reticulum (ER) stress response. Results show that resveratrol exerts its chemotherapeutic effect on human MM cells through mechanisms involving the impairment of the pro-survival XBP1 signaling and the activation of pro-apoptotic ER stress response (Wang FM, et. al., Exp Hematol 39:999-1006, 2011).

Members