Bcr-Abl tyrosine kinase inhibitors- current status

Mughal, Anum; Aslam, Hafiz Muhammad; Khan, Abdul Hameed; Saleem, Saima; Umah, Ribak; Saleem, Maria

doi:10.1186/1750-9378-8-23

Cited by 29 publications

(24 citation statements)

References 26 publications

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“…Simplified schematic diagram of the cMET pathway and the main strategies for targeted therapy. Binding of hepatocyte growth factor (HGF)/scatter factor (SF) to cMET leads to the activation of multisteps in the signal transduction cascade, which regulates cell proliferation, survival, cytoskeletal and mobility signals (24)(25)(26)(27)(28)(29). cMET signaling can be disrupted at different levels, from the cMET receptor to the downstream pathway.…”

Section: The Role Of Cmet In Gastric Cancermentioning

confidence: 99%

cMET as a potential therapeutic target in gastric cancer (Review)

Lü

2013

International Journal of Molecular Medicine

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Abstract. Gastric cancer is one of the most common malignancies worldwide. Despite improvements in surgery and chemotherapy, the outcomes in patients with advanced gastric cancer remain poor. cMET is a member of the receptor tyrosine kinase family, and plays a key role in tumor survival, growth, angiogenesis and metastasis. cMET overexpression and/or gene amplification occurs in a significant proportion of gastric cancers. cMET is associated with a high tumor stage and poor prognosis. Several cMET inhibitors have been investigated in clinical trials, and the initial results are encouraging. It has become increasingly apparent that cMET is a promising therapeutic target in gastric cancer. In this review, we summarize the development of cMET inhibitors in the preclinical and clinical environment. In addition, we discuss the challenges of cMETtargeted therapy in gastric cancer and explore possible solutions.

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Section: The Role Of Cmet In Gastric Cancermentioning

confidence: 99%

cMET as a potential therapeutic target in gastric cancer (Review)

Lü

2013

International Journal of Molecular Medicine

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“…CML is characterized by three phases, chronic phase (CP), accelerated phase and blast phase; CML usually presents in the CP. 3,4 The earlier treatment for CML with splenic radiation and conventional chemotherapy, namely hydroxyurea and busulfan, had limited effect on survival. The first breakthrough in treatment of CML was the introduction of allogeneic hematopoietic cell transplantation (HCT), which is a potentially curative treatment; however, HCT comes at the cost of increased morbidity and mortality, despite the possibility of cure.…”

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confidence: 99%

“…BCR independent resistance occurs either due to overexpression of P-glycoprotein efflux pump, activation of Src family kinase or may be because of low expression, activity or polymorphism of OCT1. 4,8 This has led to the development of additional sec- Current studies investigating TKI for chronic CML compare TKI prototype, imatinib, versus each individual secondgeneration TKI, with no head-to-head trials to compare those second-generation TKI to each other. In our study, we sought to summarize the evidence of TKI efficacy, comparing second-generation TKI directly and in-directly in patients with newly diagnosed chronic-phase CML.…”

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confidence: 99%

Tyrosine kinase inhibitors as a first‐line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed‐treatment comparison

Firwana

Sonbol

Diab

et al. 2015

Intl Journal of Cancer

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Tyrosine kinase inhibitors (TKI) are the initial treatment for majority of newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase (CP) and are associated with marked improvement in hematological, cytogenetic, molecular response and survival rates compared with other therapies. In this review, we summarize the evidence of TKI efficacy for patients with newly diagnosed CP-CML. Six trials at low risk of bias evaluating TKIs as an initial treatment in adults with newly diagnosed CP-CML and enrolling 2,456 patients were included. Follow-up times ranged from a median of 3 months to 5 years. Direct comparison showed statistically higher rates of major molecular response (MMR 0.1% IS ) achievement with second-generation TKIs at 12 months which was sustained throughout treatment period. Bayesian mixed-treatment comparison (MTC) analysis demonstrated superiority of both nilotinib and dasatinib over imatinib in terms of efficacy. Nilotinib was associated with higher deeper molecular responses (MR 4.5 0.0032% IS ) at 60 months than dasatinib but no difference in MMR. The differences between nilotinib and dasatinib are likely clinically trivial. Among TKIs, nilotinib was found to have the best survival profile. Both nilotinib and dasatinib are associated with significantly better MMR compared to imatinib that is sustained over 60 months. This analysis shows that new-generation TKIs are not only showing faster response but also maintaining a more potent one through longer follow-up period. It is important to note out that MTC is not a substitute for well-conducted RCTs investigating direct comparisons.Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm of blood stem cells. It accounts for 10-15% of new leukemia diagnoses with 5,980 new cases expected each year. 1 CML is associated with a reciprocal chromosomal translocation between the ABL oncogene on chromosome 9 and the BCR on chromosome 22.2 BCR-ABL oncoprotein has active ABL tyrosine kinase activity which leads to cell cycle deregulation, affecting differentiation and DNA repair, which results in increased proliferation, resistance to apoptosis and an alteration of their adhesion properties, and eventually leads to

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“…Nilotinib, Dasatinib, Bosutinib and Ponatinib are newer drugs of this class approved for the treatment of imatinib resistant or intolerant CML [10,11].…”

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confidence: 99%

Novel anticancer agents in clinical and preclinical trials

Salim

2014

El Med J

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Bcr-Abl tyrosine kinase inhibitors- current status

Cited by 29 publications

References 26 publications

cMET as a potential therapeutic target in gastric cancer (Review)

cMET as a potential therapeutic target in gastric cancer (Review)

Tyrosine kinase inhibitors as a first‐line treatment in patients with newly diagnosed chronic myeloid leukemia in chronic phase: A mixed‐treatment comparison

Novel anticancer agents in clinical and preclinical trials

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