Keeping one step ahead of cancer cells

BRD4 inhibitors are among the most promising new agents in cancer therapy that are currently evaluated in clinical trials. In a new study, a team of researchers reveals how leukemia cells can evade the deadly effects of BRD4 inhibition. Understanding this adaptation process could aid the development of sequential therapies to outsmart resistant leukemias.
Source: ScienceDaily Headlines - Category: Science Source Type: news

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Publication date: 10 December 2018Source: Cancer Cell, Volume 34, Issue 6Author(s): Delphine Merino, Gemma L. Kelly, Guillaume Lessene, Andrew H. Wei, Andrew W. Roberts, Andreas StrasserDefects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only pr...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
ang Leung Lysine-specific demethylase 1A (LSD1, also named KDM1A) is a demethylase that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. Pharmacological inhibition of LSD1 has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of LSD1, its role in carcinogenesis, a comparison of...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Conditions:   Acute Myelogenous Leukemia;   Acute Lymphocytic Leukemia;   Myelodysplastic Syndromes;   Non-Hodgkin Lymphoma;   Hodgkin Disease Interventions:   Procedure: Stem cell transplantation;   Drug: Itacitinib;   Other: Functional Assessment of Cancer Therapy-Bone Marrow Transplant;   Other: Human Activity Profile Sponsors:   Washington University School of Medicine;   Incyte Corporation Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
We report the rapid development of resistance in chronic lymphocytic leukemia cells isolated from patients exposed to increasing doses of Navitoclax (ABT-263), a BH3 mimetic. To mimic such rapid development of chemoresistance, we have developed simple resistance models to three different BH3 mimetics, targeting BCL-2 (ABT-199), BCL-XL (A-1331852) or MCL-1 (A-1210477), in relevant haematological cancer cell lines. In these models, resistance could be attributed neither to consistent changes in expression levels of the anti-apoptotic proteins nor interactions among different pro- and anti-apoptotic BCL-2 family members. Usin...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred.Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Canc...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I Source Type: research
Conclusion: Taken together, our data suggest that BAFF-R is amenable to CAR T-cell therapy and that targeting it may add to existing alternative strategies to overcome relapse from CD19 antigen loss, such as CD22 CAR T cells. Future strategies combining dual targeting of CD19 and BAFF-R may also be effective.DisclosuresWang: Mustang Therapeutics: Other: Licensing Agreement, Patents &Royalties, Research Funding. Forman: Mustang Therapeutics: Other: Licensing Agreement, Patents &Royalties, Research Funding.
Source: Blood - Category: Hematology Authors: Tags: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster I Source Type: research
In this study, we interrogated the US Surveillance Epidemiology and End Results (SEER) registry to analyze the risks of ALL in cancer patients treated with RT, CT or combined modality regimens at the population level.MethodsWe used our previously validated R program, SEERaBomb (Leukemia 2016; 30: 285-94) to query all 18 SEER registries, 1973-2014. We identified all first cancer cases treated with RT and/or CT that subsequently developed ALL ≥1 year after diagnosis of the first cancer. First cancer cases of lymphoid lineage were excluded. Diagnosis was derived from the International Classification of Diseases. Relative r...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Improving Outcomes with Cellular Therapy Source Type: research
Introduction: Survival rates continue to improve after allogeneic HCT (Gooley et al, NEJM, 2013). Population-based studies also indicate overall improvement in survival of older (60-80 years old) AML patients (pts) (Bower, Blood Cancer Journal, 2016). Yet, only a small minority (6%-8%) of them receive HCT (Medeiros, Ann Hematol. 2015). Given these potentially incongruent findings and the changing face of survival in AML, we designed the first prospective multi-center longitudinal study dating from first presentation of adults with AML to be treated at one of 13 different referral centers that provide both AML treatment and...
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: To Transplant or Not to Transplant? That Is the Question Source Type: research
Background: Consensus guidelines recommend anticoagulation for 3 months in patients with upper extremity catheter-related thrombosis (CRT); however, recommendations are primarily extrapolated from data on provoked lower extremity thrombosis. Many patients with hematologic malignancy are treated with shorter durations of anticoagulation due to thrombocytopenia and other bleeding concerns. It is not known if duration of anticoagulation in patients with hematologic malignancy patients and CRT predicts risk of recurrence or hemorrhage.Methods: We performed a multicenter retrospective cohort study at five institutions through t...
Source: Blood - Category: Hematology Authors: Tags: 332. Antithrombotic Therapy: Poster I Source Type: research
The hematopoietic system is one of the most well-studied and well-characterized differentiation hierarchies in the mammalian body, and hematopoiesis has for decades served as a paradigm for how stem cells generate complex, self-renewing tissues and maintain them under homeostatic, physiological stress and regenerative conditions. The hematopoietic stem cell (HSC) plays a central role in all of these scenarios: HSCs provide the developmental origin of definitive hematopoiesis, sustain baseline blood cell production and are activated in response to physiological stress. In addition, HSC are capable of regenerating the hemato...
Source: Blood - Category: Hematology Authors: Tags: Thrombopoiesis Revised: From Lung to Hematopoietic Stem Cell Platelet Bias Source Type: research
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