期刊
BLOOD ADVANCES
卷 3, 期 24, 页码 4326-4335出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019000937
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资金
- Robert H. Allen Chair in Hematology Research
- University of Colorado Department of Medicine Early Career Scholars Program
- Leukemia and Lymphoma Society's Scholar in Clinical Research award
- Cancer Biology from the National Institutes of Health, National Cancer Institute [T32CA190216]
- Conquer Cancer Foundation Young Investigator Award
- Lymphoma Research Foundation Clinical Research Mentoring Program Award
- National Institutes of Health, National Cancer Institute [R01CA235622]
Venetodax is a specific B-cell lymphoma-2 (BCL-2) inhibitor that can restore activation of apoptosis in malignancies, the survival of which depends on dysregulation of this pathway. Preclinical data, using various model systems including cell lines and patient samples, suggested targeting BCL-2 could be a successful therapeutic strategy in patients with acute myeloid leukemia (AML). As predicted by this work, the use of venetoclax in the clinical setting has resulted in promising outcomes for patients with this disease. Although venetoclax showed limited activity as a single agent in the relapsed disease setting, recent studies have shown that when combined with a backbone therapy of a hypomethylating agent or low-dose cytarabine, high response rates with encouraging remission durations for older patients with newly diagnosed AML who were not candidates for intensive induction chemotherapy were observed. Furthermore, venetodax-based therapies allowed for rapid responses and were able to effectively target the leukemia stem cell population. Here we review the preclinical data that supported the development of venetoclax in AML, as well as the results of the promising clinical trials.
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