Therapeutics and Diagnostics for Hematopoietic and Cancer Stem Cell

The self-renewal associated with cancer is based in the regenerative properties of what are now known to be “cancer stem cells” (CSC) and mutations in components of the Wnt signaling pathway are associated with the aberrant development of specific cancers.  In addition, the Wnt pathway appears to play a critical role in the growth and maintenance of normal stem or progenitor cells in a number of tissues. These features have driven interest in modulating signaling in this pathway during normal and cancer stem cell development.

Technology: UC Inventors have described the first negatively-regulating mutation in the Wnt pathway. This mutation is associated with the advanced phase of chronic myelogenous leukemia.  Xenotransplantation of such mutated cancer stem cells led to high level engraftment, quantifiable shifts in myeloid populations and altered expression of proteins relevant to the Wnt/ b-catenin signaling pathway. Proprietary methods may be used to:

• design antibodies and small molecules to diagnose, monitor and treat cancers associated with aberrant Wnt signaling, e.g. liver and colon
• provide a model for testing drugs that affect hematopoiesis
• assess drug toxicity toward stem cell, hematopoietic differentiation and proliferation and
• test novel therapeutics against this new target and other components of the Wnt/b-catenin pathway

In the field of cancer therapeutics, patient populations are increasingly resistant to drugs targeting ABL tyrosine kinase. It is clear that alternative targets with demonstrated utility will drive the development of new classes of therapeutic molecules.

Patents pending

Research Interest:  http://cancer.ucsd.edu/summaries/cjamieson.asp

Publications:
Jamieson CH, et. al., Chronic versus acute myelogenous leukemia: a question of self-renewal, Cancer Cell 2004 6(6):531-3.

Jamieson CH, et. al., Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N Engl J Med. 2004 351(7):657-67.

Passegue E, et. al., Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci U S A. 2003 100 Suppl 1:11842-9, Review.

Traggiai, E. et. al., Development of a human adaptive immune system in cord blood cell- transplanted mice. Science. 2004 304(5667):104-7.

Reya, T. and H. Clevers Wnt Signaling in Stem Cells and Cancer  Nature  434(7035):843-50

Case No: SD2007-099
Keywords: Wnt, catenin, pathogenesis, tumor, cancer, mutation, hyperproliferation, self-renewal, stem cell, hematopoiesis, blood cell
Inquiries To:  invent@ucsd.edu