A5052380534- Fibroblast Growth Factor Research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Eosinophilic Disorders and Syndromes
- Gastrointestinal Tumor Research and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Kruppel-like factors research
- Soft tissue tumor case studies
- PI3K/AKT/mTOR signaling in cancer
- Sarcoma Diagnosis and Treatment
- Extracellular vesicles in disease
- Gastrointestinal disorders and treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Protein Degradation and Inhibitors
- Cell Adhesion Molecules Research
- Lymphoma Diagnosis and Treatment
- HIV/AIDS drug development and treatment
- Neurofibromatosis and Schwannoma Cases
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Folate and B Vitamins Research
- Hemoglobinopathies and Related Disorders
- DNA and Nucleic Acid Chemistry
Dana-Farber Cancer Institute
2021-2024
Harvard University
2023-2024
Oregon Health & Science University
2013-2019
Cancer Institute (WIA)
2014
OHSU Knight Cancer Institute
2014
Potent FLT3 inhibitors, such as quizartinib (AC220), have shown promise in treating acute myeloid leukemia (AML) containing internal tandem duplication (ITD) mutations. However, responses are not durable and resistance develops within months. In this study, we outline a two-step model of whereby extrinsic microenvironmental proteins ligand (FL) fibroblast growth factor 2 (FGF2) protect FLT3-ITD+ MOLM14 cells from AC220, providing time for subsequent accumulation ligand-independent...
Kinase inhibitors such as imatinib have dramatically improved outcomes for patients with gastrointestinal stromal tumor (GIST), but many develop resistance to these treatments. Although in some this event corresponds mutations the GIST driver oncogenic kinase KIT, other without KIT mutations. In study, we address patient subset reporting a functional dependence of on FGF receptor FGFR3 and its crosstalk cells. Addition ligand FGF2 cells restored phosphorylation during treatment, allowing...
Protective signaling from the leukemia microenvironment leads to cell persistence, development of resistance, and disease relapse. Here, we demonstrate that fibroblast growth factor 2 (FGF2) bone marrow stromal cells is secreted in exosomes, which are subsequently endocytosed by cells, protect tyrosine kinase inhibitors (TKIs). Expression FGF2 its receptor, FGFR1, both increased a subset lines primary AML stroma; FGF2/FGFR1 associated with exosome secretion. FGFR inhibition (or gene...
The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases expression synergizes venetoclax in preclinical models. This dose escalation study evaluated voruciclib patients previously treated hematologic malignancies (NCT03547115)....
Abstract Introduction: CPX-351 (Vyxeos) is a liposomal combination of cytarabine and daunorubicin at synergistic 5:1 molar ratio. Recently, has been shown to be significantly more effective than the 7+3 standard care chemotherapy in treating high-risk AML patients, including patients with FLT3-ITD mutation. We previously treated primary patient samples ex vivo found that FLT3-ITD+ were sensitive showed enhanced drug uptake. hypothesized dysregulated FLT3 signaling results an activation...
Abstract Introduction: Activating mutations in the FLT3 kinase are present ∼25% of newly diagnosed acute myeloid leukemia (FLT3+ AML) patients and confer a poor prognosis. Treatment with inhibitors is initially effective, but residual cells survive bone marrow microenvironment clinical resistance develops within months. We tested proteins from for their ability to protect FLT3-ITD+ MOLM14 AC220, found that ligand (FL) fibroblast growth factor 2 (FGF2) were among most protective. Results:...
<div>Abstract<p>Kinase inhibitors such as imatinib have dramatically improved outcomes for patients with gastrointestinal stromal tumor (GIST), but many develop resistance to these treatments. Although in some this event corresponds mutations the GIST driver oncogenic kinase KIT, other without KIT mutations. In study, we address patient subset reporting a functional dependence of on FGF receptor FGFR3 and its crosstalk cells. Addition ligand FGF2 cells restored phosphorylation...