A5034963668- Prostate Cancer Treatment and Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Eosinophilic Disorders and Syndromes
- Estrogen and related hormone effects
- Genetic factors in colorectal cancer
- Radiopharmaceutical Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Prostate Cancer Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Hormonal and reproductive studies
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- HER2/EGFR in Cancer Research
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
Memorial Sloan Kettering Cancer Center
2016-2025
Howard Hughes Medical Institute
2016-2025
Kettering University
2014-2025
Newcastle University
2002-2025
University of California, Los Angeles
2002-2023
New York Genome Center
2020-2023
Molecular Oncology (United States)
2023
American Association For Cancer Research
2018-2021
Jackson Laboratory
2020
Icahn School of Medicine at Mount Sinai
2020
BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since activity essential to the transforming function of BCR-ABL, an inhibitor could be effective treatment for CML.
BCR-ABL, a constitutively activated tyrosine kinase, is the product of Philadelphia (Ph) chromosome. This enzyme present in virtually all cases chronic myeloid leukemia (CML) throughout course disease, and 20 percent acute lymphoblastic (ALL). On basis substantial activity inhibitor patients phase, we evaluated STI571 (formerly known as CGP 57148B), specific BCR-ABL who had CML blast crisis with Ph-chromosome–positive ALL.
Metastatic prostate cancer is treated with drugs that antagonize androgen action, but most patients progress to a more aggressive form of the disease called castration-resistant cancer, driven by elevated expression receptor. Here we characterize diarylthiohydantoins RD162 and MDV3100, two compounds optimized from screen for nonsteroidal antiandrogens retain activity in setting increased receptor expression. Both bind greater relative affinity than clinically used antiandrogen bicalutamide,...
Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, product of Philadelphia chromosome. Imatinib mesylate, formerly STI571, a selective inhibitor this kinase.
Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL domain point mutations that interfere with drug binding. Crystallographic studies predict most imatinib-resistant mutants should remain sensitive inhibitors bind less stringent conformational requirements. BMS-354825 is an orally bioavailable two-log increased potency relative retains activity against 14 of 15 mutants. prolongs...
The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosome-positive (Ph-positive) leukemias, but relapse occurs, mainly as a result of the outgrowth leukemic subclones with imatinib-resistant mutations. We evaluated dasatinib, that targets most mutations, patients chronic myelogenous leukemia (CML) or Ph-positive acute lymphoblastic (ALL).Patients various phases CML ALL who could not tolerate were resistant to enrolled phase 1 dose-escalation study. Dasatinib (15...
The AACR Project GENIE is an international data-sharing consortium focused on generating evidence base for precision cancer medicine by integrating clinical-grade genomic data with clinical outcome tens of thousands patients treated at multiple institutions worldwide. In conjunction the first public release from approximately 19,000 samples, we describe goals, structure, and standards report conclusions high-level analysis initial phase data. We also provide examples utility data, such as...
The progression of chronic myelogenous leukemia (CML) to blast crisis is supported by self-renewing leukemic stem cells. In normal mouse hematopoietic cells, the process self-renewal involves beta-catenin-signaling pathway. We investigated whether cells in CML also use beta-catenin pathway for self-renewal.We used fluorescence-activated cell sorting isolate common myeloid progenitors, granulocyte-macrophage and megakaryocyte-erythroid progenitors from marrow during several phases marrow....
Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence germline among men localized cancer who unselected for family predisposition is insufficient to warrant routine testing, frequency patients metastatic has not been established.
The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response EGFR kinase inhibitors. mechanism responsiveness glioblastomas these inhibitors unknown.
Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about impact this heterogeneity on clinical outcome. Here, we report and transcriptomic analysis 429 patients with castration-resistant (mCRPC) linked longitudinal outcomes, integrating findings from whole-exome, transcriptome, histologic analysis. For 128 treated a first-line next-generation androgen receptor signaling inhibitor (ARSI;...