Ivosidenib to treat adult patients with relapsed or refractory acute myeloid leukemia.

Ivosidenib to treat adult patients with relapsed or refractory acute myeloid leukemia. Drugs Today (Barc). 2020 Jan;56(1):21-32 Authors: Pasquier F, Lecuit M, Broutin S, Saada S, Jeanson A, Penard-Lacronique V, de Botton S Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to alpha-ketoglutarate (alphaKG). Somatic point mutations in IDH1/2 that are found in rare distinct subsets of cancers confer a gain of function in cancer cells which results in the accumulation and secretion in vast excess of the oncometabolite D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis. High levels of D-2HG inhibit alphaKG-dependent dioxygenases including histone, DNA and RNA demethylases, resulting in histone, DNA and RNA hypermethylation and cell differentiation blockade. In addition, D-2HG is a biomarker suitable for the detection of IDH1/2 mutations at diagnosis, and is also predictive of clinical response. The U.S. Food and Drug Administration (FDA) approved ivosidenib, a mutant-IDH1 enzyme inhibitor, for patients with relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) in 2018, and also as front-line therapy for newly diagnosed elderly patients 75 years or older or who are ineligible to receive intensive chemotherapy in 2019. Ivosidenib represents a novel drug class for targeted therapy in AML. PMID: 32055...
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

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Abstract TET family members (TETs) encode proteins that represent crucial factors in the active DNA demethylation pathway. Evidence has proved that TET2 mutation is associated with leukemogenesis, drug response, and prognosis in acute myeloid leukemia (AML). However, few studies revealed the TETs expression and its clinical significance in AML. We conducted a detailed expression and prognosis analysis of TETs expression in human AML cell lines and patients by using public databases. We observed that TETs expression especially TET2 and TET3 was closely associated with AML among various human cancers. TET1 expressio...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Cancers, Vol. 12, Pages 773: Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia Before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study Cancers doi: 10.3390/cancers12040773 Authors: Sarah Bertoli Pierre-Yves Dumas Emilie Bérard Laetitia Largeaud Audrey Bidet Eric Delabesse Suzanne Tavitian Noémie Gadaud Thibaut Leguay Harmony Leroy Jean-Baptiste Rieu Jean-Philippe Vial François Vergez Nicolas Lechevalier Isabelle Luquet Emilie Klein Audrey Sarry Anne-Charlotte De Grande Christian Récher ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemother...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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
Authors: Feng Z, Chen Q Abstract Acute myeloid leukemia is a common hematological malignancy that often exhibits strong drug resistance when treated using conventional chemotherapy. Although numerous studies have been carried out to develop methods of overcoming drug resistance, the results have generally been unsatisfactory. CD40 ligand (CD40L) has been shown to improve the sensitivity of cancer cells to drug treatment. In the present study, Adriamycin (ADM)-resistant human monocytic THP-1 cells (THP-1/A cells) were developed by incubating THP-1 cells with increasing concentrations of ADM. Cells were transfected w...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
The F-box and WD repeat domain-containing (FBXW) proteins play an important role in ubiquitin proteasome by inducing protein degradation. Ten FBXW proteins have been identified in humans. The functions of FBXW proteins, like FBXW7, have been well-established in many human cancers. However, little is known about their transcriptional expression profiles and relationship with prognosis in acute myeloid leukemia (AML). Here we investigated the roles of FBXW proteins in AML by analyzing their mRNA expression profiles and association with clinical features using data from EMBL-EBI, the Cancer Cell Line Encyclopedia, Gene Expres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThe in vitro chemosensitivity as tested by ATP-TCA demonstrated a significant correlation with CR for chemotherapy and can be a useful tool to optimize personalized treatments for patients with AML.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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