Abstract IA01: Targeting developmental pathways in cancer

Signaling pathways such as Notch, Wnt, Hedgehog, and Hippo play critical roles during embryonic development through modulation of proliferation, cell migration, and differentiation. In adults, these pathways remain important in regulating stem cell function during normal tissue homeostasis. However, inappropriate activation either through mutation or misexpression can result in tumorigenesis, making potential targets for the development of novel targeted therapeutics. The Hedgehog pathway provides a textbook example of this scenario where aberrant activation of the pathway through Patched (PTCH) loss of function mutations or Smoothened (SMO) activating mutation leads to the development of various types of cancers such as basal cell carcinoma or medulloblastoma. These observations drove the development of Hedgehog pathway inhibitors (HPI) for the treatment of various cancers, resulting in the approval of two SMO inhibitors, vismodegib and sonidegib, for the treatment of advanced BCC. Lessons learned from targeting the Hedgehog pathway may inform the development of future therapies. Citation Format: Frederic de Sauvage. Targeting developmental pathways in cancer [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr IA01.