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Hematopoietic stem cell transplantation is the standard of care for the treatment of many hematologic malignancies, including leukemias, and non-malignant diseases such as bone marrow failure. These diseases are commonly treated using chemotherapy conditioning, which has many associated adverse effects.
Dr. Zheng has developed a technology that eliminates the need for high-intensity chemotherapy conditioning. He has identified a lead Cdc42 inhibitor (CASIN) that targets the Rho GTPase Cdc42, known for maintaining stem cells in the bone marrow niche.
• Pre-treatment conditioning to prime the bone marrow environment and optimize transplant outcomes.
• Combination therapy to improve chemotherapeutic access to malignant cells (including leukemias, high risk solid tumors, lymphoma, and other blood disorders).
• Eliminates high-intensity chemotherapy conditioning
• Improves efficacy of existing chemotherapeutic regimens
• Improves engraftment
• No adverse effects
For an in-depth market overview, please click here
• More than 1.1 million people in the US are
suffering from hematologic malignancies.
• Worldwide total cost of cancer has been
estimated to be as high as $895 billion.
• Hematopoietic stem cell transplantation can be
used to treat several cancers and other diseases, with more than 50,000
transplants worldwide each year and growing.
• Stem cell mobilization failures with traditional
strategies are common and often result in delays in treatment and increased cost
and resource utilization. The utility of all current mobilization regimens is
limited by their high failure rates, which are estimated to be between 5% and 30%.
• The stem cell therapeutic market is forecast to
reach $8.9 billion by 2020.
PCT Application PendingPCT/US2014/013444Priority Date: 01/29/2013
Yi Zheng, PhDDirector, Division of Experimental Hematology and Cancer BiologyCo-Director, Cancer and Blood Diseases InstituteProfessor, UC Department of Pediatrics
View all publications associated with this technology below:
Shang X, Marchioni F, Evelyn CR, Sipes N, Zhou X, Seibel W,
Wortman M, Zheng Y. Small-molecule inhibitors targeting G-protein-coupled Rho
guanine nucleotide exchange factors. Proc Natl Acad Sci U S A. 2013 Feb
Shang X, Zheng Y. Rational design of Rho GTPase-targeting inhibitors. Methods Mol Biol. 2012;928:29-38.
Shang X, Marchioni F, Sipes N, Evelyn CR, Jerabek-Willemsen
M, Duhr S, Seibel W, Wortman M, Zheng Y. Rational design of small molecule inhibitors targeting RhoA subfamily Rho GTPases. Chem Biol. 2012 Jun
Liu W, Feng Y, Shang X, Zheng Y. Rho GTPases in
hematopoietic stem/progenitor cell migration. Methods Mol Biol. 2011;750:307-19.
Shang X, Cancelas JA, Li L, Guo F, Liu W, Johnson JF, Ficker
A, Daria D, Geiger H, Ratner N, Zheng Y. R-Ras and Rac GTPase cross-talk regulates hematopoietic progenitor cell migration, homing, and mobilization. J Biol Chem. 2011 Jul 8;286(27):24068-78.
Stengel K, Zheng Y. Cdc42 in oncogenic transformation,invasion, and tumorigenesis. Cell Signal. 2011 Sep;23(9):1415-23.
Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng
Y. Rho GTPases in hematopoiesis and
hemopathies. Blood. 2010 Feb 4;115(5):936-47.
Yang L, Zheng Y. Cdc42: a signal coordinator in
hematopoietic stem cell maintenance. Cell Cycle. 2007 Jun 15;6(12):1445-50.
Yang L, Wang L, Geiger H, Cancelas JA, Mo J, Zheng Y. RhoGTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow. Proc Natl Acad Sci U S A. 2007 Mar
Ghiaur G, Lee A, Bailey J, Cancelas JA, Zheng Y, Williams
DA. Inhibition of RhoA GTPase activity enhances hematopoietic stem and progenitor cell proliferation and engraftment. Blood. 2006 Sep
Wang L, Yang L, Filippi MD, Williams DA, Zheng Y. Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment. Blood. 2006 Jan 1;107(1):98-105.
Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y,
Williams DA. Rac GTPases differentially integrate signals regulating
hematopoietic stem cell localization. Nat Med. 2005 Aug;11(8):886-91.
Debidda M, Wang L, Zang H, Poli V, Zheng Y. A role of STAT3in Rho GTPase-regulated cell migration and proliferation. J Biol
Chem. 2005 Apr29;280(17):17275-85.
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