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
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Ruvolo, Peter P; Ruvolo, Vivian R; Benton, Christopher B et al. (2016) Combination of galectin inhibitor GCS-100 and BH3 mimetics eliminates both p53 wild type and p53 null AML cells. Biochim Biophys Acta 1863:562-71
Takahashi, Koichi; Kantarjian, Hagop; Garcia-Manero, Guillermo et al. (2016) Clofarabine Plus Low-Dose Cytarabine Is as Effective as and Less Toxic Than Intensive Chemotherapy in Elderly AML Patients. Clin Lymphoma Myeloma Leuk 16:163-8.e1-2
Zeng, Zhihong; Wang, Rui-Yu; Qiu, Yi Hua et al. (2016) MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/ progenitor cells. Oncotarget 7:55083-55097

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