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Project B1: Small molecule-induced reprogramming of pancreatic tumor and stroma compartments

Participants:

Prof. Dr. Wibke Diederich
School of Pharmacy
Center for Tumor- and Immune Biology (ZTI)
Philipps-Universität Marburg

Prof. Dr. Matthias Lauth
Institute of Molecular Biology and Tumor Research
Center for Tumor- and Immune Biology (ZTI)
Philipps-Universität Marburg

Project aims:

Pancreatic cancer is characterized by a strong desmoplastic reaction, which is mainly due to the deposition of ECM by activated stellate cells. The Hedgehog (Hh) signaling pathway is central to the development of this fibrotic reaction and the Hh-activated stroma was recently shown to restrain cancer growth and promote tumor cell differentiation. In addition to these microenvironment-induced effects, cell-intrinsic mechanisms exist which maintain the generally dedifferentiated state of tumor cells. In this project proposal, we wish to employ a novel pharmacological approach, which would target both tumor compartments by modulating the stromal as well as the cancer cell-intrinsic mechanisms of differentiation. We wish to validate this hitherto unknown epigenetic reprogramming approach targeting the tumor and stroma compartments in in vitro and in vivo assays and increase the drug-like properties of this compound by medicinal chemistry efforts for later preclinical investigations.