Search results for "Tyro"

Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial

2020

Abstract The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P = .044). A trend toward improved …

Improvement in Lung Cancer Outcomes With Targeted Therapies: An Update for Family Physicians.

2015

Abstract: In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. Family physicians play an important role in the treatment, detection, and management of common toxicities and…

High BCR-ABL Levels At Diagnosis Are Associated with Unfavorable Responses to Imatinib Mesylate.

2012

Abstract Abstract 2790 The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated a need for early molecular parameters associated with inadequate responses to Imatinib Mesylate (IM). Recent evidence suggests that CML patients presenting BCR-ABL/ABLIS levels >10% after 3 months of IM or >1% after 6 months of treatment have inferior outcomes in terms of both overall survival (OS) and progression-free survival. We wanted to establish if high BCR-ABL transcripts at diagnosis would also be associated with unfavorable responses to IM. To this end, we correlated quantitative determinations of BCR-ABL measu…

Prognostic and predictive biomarkers for targeted therapy in NSCLC: For whom the bell tolls?

2015

Introduction: The discovery of molecular biomarkers and the advent of targeted therapies have led to a radical change in the treatment of several tumors, including NSCLC. In the last few years, the number of molecular biomarkers has rapidly increased, and a growing interest has been recently focused on their potential prognostic and predictive value in clinical settings. Areas covered: This review describes all the molecular biomarkers with prognostic and predictive value in NSCLC, including both clinically approved biomarkers, and emerging biomarkers under investigation in clinical trials. Liquid biopsy and applications of circulating biomarkers are also described. Expert opinion: The onco…

Looking for a new panacea in ALK-rearranged NSCLC: may be Ceritinib?

2014

Abstract: In the past decade, the advent of targeted therapy led to a silent revolution in the war against lung cancer and a significant evolution on the concept of Phase I clinical trials design. Thanks to the specificity of their target, the new drugs have radically changed NSCLC treatment, leading to the development of personalized strategies. The accelerated approval of the first ALK-inhibitor, Crizotinib and more recently Ceritinib, without a Phase III randomized, clinical trial, has been an amazing success story in lung cancer research, marking the beginning of a new decade of targeted drugs development, characterized by modern, biomarker-driven, early clinical trial design and shorte…

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

2020

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI an…

Risk factors and molecular characterization of penile cancer

2020

Purpose of review To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa). Recent findings E2F, LAMC2, MAML2, ID1 and IGFBP2 proteins were demonstrated to play a critical role for aggressive tumor behavior and might predict poor survival in PeCa. PD-L1 axis was confirmed as a promising pathway to serve as a therapeutic target. A number of genetic alterations were illuminated. In clinical testing, pan-HER tyrosine kinase inhibitor dacomitinib provided promising results in chemo-naive and EGFR monoantibody nimotuzumab i…

The role of second and third line tyrosine kinase inhibitor monotherapy in EGFR wild-type (and unknown mutational status) advanced non-small-cell lun…

2015

Rituximab in AChR subtype of myasthenia gravis: systematic review

2020

Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine …

285 DOWNREGULATION OF ORGANIC CATION TRANSPORTERS OCT1 (SLC22A1) AND OCT3 (SLC22A3) IN HUMAN HEPATOCELLULAR CARCINOMA AND THEIR PROGNOSTIC SIGNIFICAN…

2012

Background Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).