Frederic J. de Sauvage
Genentech
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
Member
(elected 2022)
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Biosketch
Frederic de Sauvage is a molecular oncologist recognized for his work on targeting oncogenic pathways for the treatment of cancer He grew up near Brussels, Belgium and obtained his BS in chemistry and a PhD in neuroscience from the Catholic University of Louvain in Belgium. He joined the laboratory of David Goeddel at Genentech as a postdoctoral fellow in 1990 and as Scientist in 1992. In 1994, de Sauvage discovered Thrombopoietin (TPO), the long sought physiological regulator of platelet production before switching his focus to the Hedgehog pathway. He identified oncogenic mutations in Smoothened, a cell surface component of the Hedgehog receptor and led the development of a small molecule inhibitor of Smoothened, vismodegib, that is approved for the treatment of advanced basal cell carcinoma. In 2011 he received the Achievement in Advancing Targeted Therapies for Cancer & Melanoma Award from the American Skin Association in recognition of his work for patients with BCC. He is a fellow of the American Association for the Advancement of Science and an EMBO Associate Member.
Research Interests
Frederic de Sauvage's laboratory is interested the role of pathways involved in development such as Wnt, Notch and Hedgehog play in cancer. Following his group's work on the Hedgehog pathway and the development of vismodegib, a small molecule inhibitor of the Hedgehog pathway approved for the treatment of advanced basal cell carcinoma, they turned their attention to the Wnt pathway in colorectal cancer (CRC). Through genomic analysis of colon tumors, his group identified translocations in R-Spondins as an alternative mechanism leading to Wnt pathway activation in CRC. Targeting R-Spondin in these tumors shows strong anti-tumor activity by inducing tumor cell differentiation all stem and progenitor compartments. Using a mouse model allowing the specific elimination of intestinal stem cells they uncovered that their loss could be compensated through mechanisms of plasticity allowing the maintenance of intestinal homeostasis. This mechanism is also at play in colon tumors where it enables tumors to rapidly adapt to the loss of the cancer stem cell compartment. While limiting the utility of targeting stem cells in established tumors, they showed that the metastatic process is critically dependent on Lgr5+ cancer stem cells in CRC.
