کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2162335 1091246 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Failure of Hypomethylating Agent-Based Therapy in Myelodysplastic Syndromes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Failure of Hypomethylating Agent-Based Therapy in Myelodysplastic Syndromes
چکیده انگلیسی
Hypomethylating agents such as 5-azacytidine or decitabine have been a major breakthrough in the treatment of patients with myelodysplastic syndromes (MDS). They have been shown to improve transfusion requirements and to change the natural history of the disease. However, with increasing cumulative clinical experience, it has become apparent that these agents are not curative and have their own shortcomings. There is a subgroup of patients who do not respond to frontline therapy and a large, growing cohort of patients that lose response or progress while on hypomethylating agent-based therapy. There are no standard treatment options in this arena and it is therefore a focus of significant research interest. Since the mechanisms of resistance to hypomethylating agents are not known, selection of therapy is largely empiric but must take into account the age, comorbidities, and performance status of the patient, as well as the characteristics of the disease at the time of treatment failure. Higher intensity approaches and allogeneic stem cell transplant can yield improved response rates and long-term disease control but should be limited to a selected cohort of patients who can tolerate the treatment-related morbidities. For the majority of patients who likely will be better candidates for lower intensity therapy, several novel, investigational approaches are becoming available. Among these are newer nucleoside analogues, inhibitors of protein tyrosine kinases, molecules that interact with redox signaling within the cell, immunotherapy approaches, and others. Patients with MDS whose disease has failed to respond to hypomethylating agent therapy should be referred for clinical trials when available. As we learn more about the patterns and mechanisms of failure, the next challenge will be to determine which therapies are suitable for each individual patient.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Seminars in Oncology - Volume 38, Issue 5, October 2011, Pages 682-692
نویسندگان
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