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Management strategies for patients with chronic lymphocytic leukaemia harbouring complex karyotype.
Br J Haematol
January 2025
Hematology Unit, Department of Medicine DIMED, University of Padua, Padova, Italy.
Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies.
View Article and Find Full Text PDFCombination of fruquintinib with venetoclax for the treatment of colorectal cancer.
Oncol Res
December 2024
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Background: As a novel blocker of vascular endothelial growth factor receptor (VEGFR), fruquintinib has been approved for treating colorectal cancer (CRC). However, its dosage and therapeutic efficacy are limited by its widespread adverse reactions. Venetoclax, recognized as the initial inhibitor of B-cell lymphoma protein 2 (BCL2), has shown potential in boosting the effectiveness of immunotherapy against CRC.
View Article and Find Full Text PDFSOHO State of the Art Updates and Next Questions | Venetoclax + Obinutuzumab Therapy in Chronic Lymphocytic Leukemia.
Clin Lymphoma Myeloma Leuk
December 2024
Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY.
In the past decade, the treatment paradigm for chronic lymphocytic leukemia (CLL) has markedly shifted from traditional chemoimmunotherapy towards targeted therapies. A fixed-duration, targeted regimen with venetoclax, a potent oral BCL-2 inhibitor, combined with obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody (Ven-Obi), has become the standard to beat for time-limited therapy in CLL. Ven-Obi allows for the rapid induction of remissions with high rates of undetectable minimal residual disease (uMRD) in patients across different treatment settings.
View Article and Find Full Text PDFNuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.
Adv Sci (Weinh)
December 2024
Department of Systems Biology, Beckman Research Institute, City of Hope, 1500 E Duarte Rd, Duarte, CA, 91010, USA.
Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.
View Article and Find Full Text PDFAdoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins.
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