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| http://dx.doi.org/10.1038/embor.2011.62 | DOI Listing |
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The CDK9 inhibitor enitociclib overcomes resistance to BTK inhibition and CAR-T therapy in mantle cell lymphoma.
Biomark Res
June 2024
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, 77030, Houston, TX, USA.
Article Synopsis
- Inhibitors of Bruton's tyrosine kinase (BTKi) and CAR-T therapy targeting CD19 have revolutionized mantle cell lymphoma (MCL) treatments, yet patients frequently experience relapses necessitating new therapeutic approaches.
- Single-cell RNA sequencing revealed that resistance development is linked to significant changes in gene expression, particularly with the MYC gene, leading researchers to explore targeting CDK9 as a potential solution.
- Enitociclib, a selective CDK9 inhibitor, demonstrated strong effectiveness against lymphoma cells, showing promise in reducing tumor growth and overcoming resistance in research models, suggesting its potential for clinical application.
Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins.
Cell Death Dis
November 2023
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells.
View Article and Find Full Text PDFA phase 1b study of venetoclax and alvocidib in patients with relapsed/refractory acute myeloid leukemia.
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Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
Relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) is a genetically complex and heterogeneous disease with a poor prognosis and limited treatment options. Thus, there is an urgent need to develop therapeutic combinations to overcome drug resistance in AML. This open-label, multicenter, international, phase 1b study evaluated the safety, efficacy, and pharmacokinetics of venetoclax in combination with alvocidib in patients with R/R AML.
View Article and Find Full Text PDFA phase 2 study of nivolumab combined with ibrutinib in patients with diffuse large B-cell Richter transformation of CLL.
Blood Adv
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Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing.
View Article and Find Full Text PDFDifferential responses of COPD macrophages to respiratory bacterial pathogens.
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Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
COPD patients have increased susceptibility to airway bacterial colonisation. and are three of the most common respiratory bacterial species in COPD. colonisation but not other bacteria, in COPD patients is associated with higher sputum neutrophil counts.
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