Abstract

) The overall aims of the Hematologic Oncology Project are to develop and test new and effective strategies for treating hematologic neoplasms using targeted therapies and biologic agents.
The SPECIFIC AIMS for this revised proposal are to: Develop novel therapeutic strategies in hematologic malignancies, including a) histone deacetylase inhibitors, such as depsipeptide b) geldanamycin in the treatment of CML c) desoxyepothiline B in the treatment of non-Hodgkin's Iymphoma. Evaluate the use of targeted therapies using: a)monoclonal antibodies in dose-intense strategies, with autologous stem cell support for myeloid leukemias and myelodysplastic syndromes, using a radio labeled humanized monoclonal antibody (HuMl95; anti-CD33) to deliver targeted radiotherapy b)monoclonal antibodies for treatment of minimal residual disease in acute promyelocytic leukemia using all-trans retinoic acid for induction, followed by unlabeled HuM195, arsenic trioxide, and then idarubicin for consolidation c) ''tumor-specific'' vaccine approaches in patients with peptide vaccine in patients with myelodysplastic syndromes or AML. Evaluate tumor specific endpoints using a)Correlative in vitro assays of HDAC inhibition b) Serial quantitative levels of BCR-ABL protein (or rnRNA) c) MR Spectroscopy to assess response (for d) RT-PCR based assays to detect residual APL cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA005826-38A1
Application #
6470066
Study Section
Project Start
1978-01-01
Project End
2005-06-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
2001
Total Cost
$188,635
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Tedeschi, Philip M; Vazquez, Alexei; Kerrigan, John E et al. (2015) Mitochondrial Methylenetetrahydrofolate Dehydrogenase (MTHFD2) Overexpression Is Associated with Tumor Cell Proliferation and Is a Novel Target for Drug Development. Mol Cancer Res 13:1361-6
Bell, Melanie L; Kenward, Michael G; Fairclough, Diane L et al. (2013) Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ 346:e8668
Zhou, Ping; Hoffman, James; Landau, Heather et al. (2012) Clonal plasma cell pathophysiology and clinical features of disease are linked to clonal plasma cell expression of cyclin D1 in systemic light-chain amyloidosis. Clin Lymphoma Myeloma Leuk 12:49-58
Rizvi, Naiyer A; Rusch, Valerie; Pao, William et al. (2011) Molecular characteristics predict clinical outcomes: prospective trial correlating response to the EGFR tyrosine kinase inhibitor gefitinib with the presence of sensitizing mutations in the tyrosine binding domain of the EGFR gene. Clin Cancer Res 17:3500-6
Zhao, Binsheng; Oxnard, Geoffrey R; Moskowitz, Chaya S et al. (2010) A pilot study of volume measurement as a method of tumor response evaluation to aid biomarker development. Clin Cancer Res 16:4647-53
Klimek, Virginia M; Fircanis, Sophia; Maslak, Peter et al. (2008) Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes. Clin Cancer Res 14:826-32
Riely, Gregory J; Kris, Mark G; Zhao, Binsheng et al. (2007) Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus. Clin Cancer Res 13:5150-5
Zhao, Binsheng; Schwartz, Lawrence H; Moskowitz, Chaya S et al. (2006) Lung cancer: computerized quantification of tumor response--initial results. Radiology 241:892-8
Maslak, P; Chanel, S; Camacho, L H et al. (2006) Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia 20:212-7
Yankeelov, Thomas E; Rooney, William D; Huang, Wei et al. (2005) Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology. NMR Biomed 18:173-85

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