Glivec Research Today is a free monthly online journal that collates and summarizes the latest research about Glivec, including details on gleevec, imatinib, cancer, treatment, side-effects.

Second-generation BCR-ABL inhibitors for frontline treatment of chronic myeloid leukemia in chronic phase.

Rosti G, Castagnetti F, Gugliotta G, Palandri F, Baccarani M

Department of Hematology and Oncology "L. and A. Seràgnoli," University of Bologna, Italy.

Results from several trials in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) of dasatinib and nilotinib, two BCR-ABL inhibitors with higher in vitro potency compared with imatinib, have recently been reported. In this review, the rationale for assessing dasatinib and nilotinib in the frontline setting is discussed and data from clinical trials performed to date are summarized, including single-arm studies and randomized trials compared with imatinib. Overall, both dasatinib and nilotinib have shown superior efficacy compared with imatinib during the first year of treatment and longer-term follow-up is needed to confirm that this superiority is maintained over time. Both agents have also shown favorable tolerability profiles, although distinct patterns of adverse events are seen with each agent. Clinicians now have several effective options to treat patients newly diagnosed with CML-CP and available data suggest that dasatinib and nilotinib represent improved therapeutic options compared with imatinib.

Published 13 May 2011 in Crit Rev Oncol Hematol.
Full-text of this article is available online (may require subscription).

Articles on Glivec published 13 May 2011:

Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation.   Blood, 117(19): 5198-206.

Dasatinib is a novel, potent, ATP-competitive inhibitor of Bcr-Abl, cKIT, and Src family kinases that exhibits efficacy in patients with imatinib-resistant chronic myelogenous leukemia. Dasatinib treatment is associated with mild thrombocytopenia and an increased risk of bleeding, but its biological effect on megakaryocytopoiesis and platelet production is unknown. In this study, we show that dasatinib causes mild thrombocytopenia in mice without altering platelet half-life, suggesting that it ... [Abstract] [Full-text]

Articles on Glivec published 12 May 2011:

Bcr-Abl kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inihibitors: recommendations from an expert panel on behalf of European LeukemiaNet.   Blood.

Mutations in the Bcr-Abl kinase domain (KD) may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in CML have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study (EUTOS) and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, ... [Abstract] [Full-text]

Imatinib elicited a favorable response in a dog with a mast cell tumor carrying a c-kit c.1523A>T mutation via suppression of constitutive KIT activation.   Vet Immunol Immunopathol.

Target therapy using the tyrosine kinase inhibitor imatinib is one of the new therapeutic approaches for canine mast cell tumors (MCTs). In the present report, we demonstrate a clinical response to imatinib in a dog with MCT carrying a c-kit c.1523A>T mutation. Moreover, the effect of this mutation on the phosphorylation status of KIT and the inhibitory potency of imatinib on the phosphorylation of the mutant KIT were examined in vitro. A dog with a MCT tumor mass on the right forelimb sole ... [Abstract] [Full-text]

Growing tumor vessels: More than one way to skin a cat - Implications for angiogenesis targeted cancer therapies.   Mol Aspects Med.

The establishment of a functional, integrated vascular system is instrumental for tissue growth and homeostasis. Without blood vessels no adequate nutrition and oxygen would be provided to cells, nor could the undesired waste products be efficiently removed. Blood vessels constitute therefore one of the largest and most complex body network whose assembly depends on the precise balance of growth factors acting in a complementary and coordinated manner with cells of several identities. However, ... [Abstract] [Full-text]

Articles on Glivec published 11 May 2011:

Advances in molecular characterization and targeted therapy in dermatofibrosarcoma protuberans.   Sarcoma, 2011: 959132.

The molecular pathogenesis of dermatofibrosarcoma protuberans (DFSP) involves distinctive rearrangement of chromosomes 17 and 22 leading to formation of the COL1A1-PDGFB fusion gene. The knowledge of molecular events underlying development of DFSP resulted in the implementation of targeted therapy with imatinib-a tyrosine kinase inhibitor (TKI), to the clinical practice. The striking efficacy of imatinib in advanced cases of DFSP has been demonstrated in a few clinical trials. Thus, imatinib is ... [Abstract] [Full-text]

HDAC Inhibitors Potentiate the Activity of the BCR/ABL Kinase Inhibitor KW-2449 in Imatinib-Sensitive or -Resistant BCR/ABL+ Leukemia Cells In Vitro and In Vivo.   Clin Cancer Res.

PURPOSE: The purpose of this study was to determine whether histone deacetylase (HDAC) inhibitors (HDACI) such as vorinostat or entinostat (SNDX-275) could increase the lethality of the dual Bcr/Abl-Aurora kinase inhibitor KW-2449 in various Bcr/Abl(+) human leukemia cells, including those resistant to imatinib mesylate (IM). EXPERIMENTAL DESIGN: Bcr/Abl(+) chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cells, including those resistant to IM (T315I, E255K), were ... [Abstract] [Full-text]

Epigenetic Silencing of MicroRNA-203 Dysregulates ABL1 Expression and Drives Helicobacter-Associated Gastric Lymphomagenesis.   Cancer Res.

Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) develops in the chronically inflamed mucosa of patients infected with the bacterial pathogen Helicobacter pylori. Here we use patient material, primary gastric lymphoma cell cultures, and a preclinical model of the disease to examine the role of microRNA (miRNA)-mediated posttranscriptional regulation-focusing in particular on miR-203 and its target ABL1-in gastric MALT lymphomagenesis. Microarray-based miRNA ... [Abstract] [Full-text]

Articles on Glivec published 10 May 2011:

A Study of Pipeline Drugs in Neuroendocrine Tumors.   J Gastrointest Cancer.

PURPOSE: Inhibition of neovessel development can stabilize tumor growth. A rapid in vitro method that can evaluate the effectiveness of anti-angiogenic drugs would aid in drug development. We tested a series of investigational agents to determine their ability to inhibit angiogenesis in our in vitro human angiogenesis model. METHODS: A total of 74 neuroendocrine tumors were tested with five therapeutic agents for anti-angiogenic activity. Angiogenic responses were assessed visually and the ... [Abstract] [Full-text]

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