Researchers pinpoint why lymphoma patients may become resistant to specific therapy

(H. Lee Moffitt Cancer Center&Research Institute) Researchers from Moffitt Cancer Center and Dana-Farber Cancer Institute have discovered a mechanism of drug resistance to Venetoclax ® , also known as ABT-199, a BCL-2 targeting drug commonly used to treat chronic lymphocytic leukemia and acute myeloid leukemia. Their findings, published in the journal Cancer Cell, also suggest a possible co-treatment strategy to overcome this resistance.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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Basel, 23 March 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the phase III VIALE-A study met its dual primary endpoints of overall survival and composite complete remission rate (CR + CRi). Venclexta ®/Venclyxto® (venetoclax) in combination with azacitidine, a hypomethylating agent, showed a statistically significant improvement in overall survival in people with previously untreated acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy, compared to azacitidine alone. Safety for Venclexta/Venclyxto plus azacitidine appeared consistent with the known safety profile ...
Source: Roche Media News - Category: Pharmaceuticals Source Type: news
hazib Pervaiz Deregulated cellular apoptosis is a hallmark of cancer and chemotherapy resistance. The B-cell lymphoma 2 (BCL-2) protein family members are sentinel molecules that regulate the mitochondrial apoptosis machinery and arbitrate cell fate through a delicate balance between pro- and anti-apoptotic factors. The recognition of the anti-apoptotic BCL2 gene as an oncogenic driver in hematological malignancies has directed attention toward unraveling the biological significance of each of the BCL-2 superfamily members in cancer progression and garnered interest in the targeting of apoptosis in cancer therapy. Acco...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Basel, 31 January 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency ’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Venclyxto® (venetoclax) in combination with Gazyvaro® (obinutuzumab) for the treatment of adults with previously untreated chronic lymphocytic leukaemia (CLL).“Despite advances in treating chronic lymphocytic leukaemia, many patients cannot tolerate the side effects of chemotherapy-containing regimens,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product ...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
ConclusionWe suggest a one ‐compartment population model with first‐order elimination to capture the pharmacokinetic profile for basiliximab for this patient population.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research
Conclusion.Progression of CLL, AML, and NHL was associated with higher health care costs over a 12‐month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types.Implications for Practice.Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non‐Hodgkin's lymphoma and compared health care costs in patients with and without evidence of di...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Leukemias, Lymphoma, Hematologic Malignancies, Health Outcomes and Economics of Cancer Care Source Type: research
AbstractApoptosis, the process of programmed cell death, occurs normally during development and aging. Members of the B-cell lymphoma 2 (BCL2) family of proteins are central regulators of apoptosis, and resistance to apoptosis is one of the hallmarks of cancer. Targeting the apoptotic pathway via BCL2 inhibitors has been considered a promising treatment strategy in the past decade. Initial efforts with small molecule BH3 mimetics such as ABT-737 and ABT-263 (navitoclax) pioneered the development of the first-in-class Food and Drug Administration (FDA)-approved oral BCL2 inhibitor, venetoclax. Venetoclax was approved for th...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis. Introduction Apoptosis is a process of cellular suicide through which unwanted or unhealthy cells are eliminated during organism development or cellular stress (Reed, 2002; Fernald and Kurokawa, 2013). Deregulated apoptosis is a characteristic of cancers (Doi et al., 2012; Roizen, 2012). The B-cell lymphoma-2 (Bcl-2) family is composed of pro- and anti-apoptotic proteins, plays pivotal role in the mitochondrial pathway of apoptosi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Yi He†, Wenyong Long† and Qing Liu* Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China Super-enhancers (SEs) refer to large clusters of enhancers that drive gene expressions. Recent data has provided novel insights in elucidating the roles of SEs in many diseases, including cancer. Many mechanisms involved in tumorigenesis and progression, ranging from internal gene mutation and rearrangement to external damage and inducement, have been demonstrated to be highly associated with SEs. Moreover, translocation, formation, deletion, or duplication of SEs themselves co...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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