It is universally acknowledged that the major problem in the management of AML is the high probability of disease recurrence. This reflects the very low likelihood of successful treatment outcome once recurrence occurs. In fact, almost invariably, outcome following application of the same treatment regimen is worst at relapse than at initial diagnosis. Reasons for the this fundamental clinical observation remain obscure. As a corollary, a major difficulty with development of new salvage therapies has been lack of understanding of the cellular targets toward which such therapies should be directed. However, in the last few years, the critical role of apoptosis in determining response to chemotherapy has been established; furthermore, some apoptotic pathways have been unraveled. These developments make it possible to design drugs targeting these pathways and thus, to demonstrate the feasibility of this approach. Knowledge of pathways involved in death of AML cells may also improve our ability to predict outcome in the regulation of cell death pathways are being studied in Projects 1-3. They include Bcl-2 and IAP family members. The Core will conduct the clinical trials designed to assess whether the ability of drugs such as antisense to bcl-2, bryostatin UCN01 and Dolastatin to modulate mediators of apoptosis parallels the clinical response to these drugs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055164-11
Application #
6664482
Study Section
Subcommittee E - Prevention &Control (NCI)
Project Start
2002-09-27
Project End
2003-06-30
Budget Start
Budget End
Support Year
11
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Ishizawa, Jo; Nakamaru, Kenji; Seki, Takahiko et al. (2018) Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition. Cancer Res 78:2721-2731
Ruvolo, Peter P; Ruvolo, Vivian R; Burks, Jared K et al. (2018) Role of MSC-derived galectin 3 in the AML microenvironment. Biochim Biophys Acta Mol Cell Res 1865:959-969
Ngankeu, Apollinaire; Ranganathan, Parvathi; Havelange, Violaine et al. (2018) Discovery and functional implications of a miR-29b-1/miR-29a cluster polymorphism in acute myeloid leukemia. Oncotarget 9:4354-4365
Le, Phuong M; Andreeff, Michael; Battula, Venkata Lokesh (2018) Osteogenic niche in the regulation of normal hematopoiesis and leukemogenesis. Haematologica :
Jiang, Xuejie; Mak, Po Yee; Mu, Hong et al. (2018) Disruption of Wnt/?-Catenin Exerts Antileukemia Activity and Synergizes with FLT3 Inhibition in FLT3-Mutant Acute Myeloid Leukemia. Clin Cancer Res 24:2417-2429
Sekihara, Kazumasa; Saitoh, Kaori; Han, Lina et al. (2017) Targeting mantle cell lymphoma metabolism and survival through simultaneous blockade of mTOR and nuclear transporter exportin-1. Oncotarget 8:34552-34564
Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng et al. (2017) Focal Adhesion Kinase as a Potential Target in AML and MDS. Mol Cancer Ther 16:1133-1144
Zeng, Zhihong; Liu, Wenbin; Tsao, Twee et al. (2017) High-throughput profiling of signaling networks identifies mechanism-based combination therapy to eliminate microenvironmental resistance in acute myeloid leukemia. Haematologica 102:1537-1548
Pan, Rongqing; Ruvolo, Vivian; Mu, Hong et al. (2017) Synthetic Lethality of Combined Bcl-2 Inhibition and p53 Activation in AML: Mechanisms and Superior Antileukemic Efficacy. Cancer Cell 32:748-760.e6
Jacamo, Rodrigo; Davis, R Eric; Ling, Xiaoyang et al. (2017) Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia. Oncotarget 8:83354-83369

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