Search results for "Nilotinib"
showing 8 items of 18 documents
Cardiovascular Damage Induced by Anti-BCR-ABL TKIs
2018
Anti-BCR-ABL TKIs (tyrosine kinase inhibitors) are drugs that inhibit BCR ABL tyrosine. They are used especially in the treatment of hematological cancer and gastrointestinal stromal tumors (GIST). Anti-BCR-ABL TKIs include first (imatinib), second (nilotinib, dasatinib, bosutinib) and third-generation drugs (ponatinib). Especially second- and third-generation drugs can cause cardiovascular complications such as arterial thrombosis, myocardial ischemia, peripheral arterial diseases, QTc prolongation, and pulmonary hypertension. Nilotinib and ponatinib can cause thrombotic arterial events with various mechanisms. Particularly dasatinib can cause pulmonary hypertension. Compared to convention…
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…
First Interim Analysis of the Italian Dante Study: De-Escalation before Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Treated wi…
2021
Abstract Introduction: Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is demonstrated to be achievable and recommended for patients (pts) in sustained deep molecular response (sDMR) who can discontinue tyrosine kinase inhibitor (TKI) treatment and maintain responses in ~50% of cases. While the feasibility and safety of TKI cessation have been largely demonstrated, the strategies of TFR optimization are yet to be clarified. Studies (eg. DESTINY) investigating de-escalation, mainly after imatinib, suggested that a stepwise approach may favor TFR outcome. We present the interim results of the phase 2, prospective, multicenter DANTE study (NCT03874858) evaluating de-escalation…
Outcome of patients with CML treated with dasatinib or nilotinib after failure of second prior TKIs.
2010
Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients …
Show me your signaling– and I’ll tell you who you are
2009
See Article, pages 725–733Cancer research and therapy have come a long way:the field started out in search of a ‘‘magic bullet” accord-ing to Paul Ehrlich’s theory, and was hoping to identifya target which was pivotal to signaling survival in trans-formed cells. Indeed, certain diseases with monocausalmutations were identified, and targeting of the muta-tional products has helped in the design of treatmentstrategies. In chronic myeloid leukemia (CML), the con-stitutive activation of the tyrosine kinase BCR-ABL ispathognomonic [1], and multiple BCR-ABL kinaseinhibitors (e.g. imatinib mesylate, dasatinib, nilotinib)have been developed and successfully used in the treat-ment of CML offering near-…
Stochastic dynamics of leukemic cells under an intermittent targeted therapy
2009
The evolutionary dynamics of cancerous cell populations in a model of Chronic Myeloid Leukemia (CML) is investigated in the presence of an intermittent targeted therapy. Cancer development and progression is modeled by simulating the stochastic evolution of initially healthy cells which can experience genetic mutations and modify their reproductive behavior, becoming leukemic clones. Front line therapy for the treatment of patients affected by CML is based on the administration of tyrosine kinase inhibitors, namely imatinib (Gleevec) or, more recently, dasatinib or nilotinib. Despite the fact that they represent the first example of a successful molecular targeted therapy, the development o…
Imatinib Mesylate and Nilotinib Affect the MHC-Class I Presentation by Modulating the Proteasomal Processing of Antigenic Peptides.
2009
Abstract Abstract 2169 Poster Board II-146 The tyrosine kinase inhibitors (TKIs) Imatinib mesylate (IM, Gleevec, Glivec) and nilotinib (Tasigna, AMN) are currently used in treatment of chronic myeloid leukaemia (CML). IM has been described to influence the function and differentiation of antigen presenting cells, to inhibit the effector function of T lymphocytes and to decrease the immunogenicity of CML cells by downregulation of tumor associated antigens. In the present study, we analyzed the effect of IM and AMN on proteasomal activity in IM-sensitive or IM/AMN- resistant CML cells as well as in patient samples using a biotinylated active site-directed probe, which, covalently binds and l…