کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8716230 | 1587880 | 2018 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
STAT3 Mediates Nilotinib Response in KIT-Altered Melanoma: A Phase II Multicenter Trial of the French Skin Cancer Network
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کلمات کلیدی
PI3Kacutely transforming retrovirus AKT8 in rodent T-cell lymphomaPDGFRpSTAT3Janus kinase - کیناز جانوس MAPK - MAPKSTAT - آمارAkt - آکتoverall survival - بقای کلgastrointestinal stromal tumors - تومورهای استرومای گوارشیPositron emission tomography - توموگرافی گسیل پوزیترونadverse event - عارضه جانبی یا عوارض جانبیconfidence interval - فاصله اطمینانphosphatidyl inositol 3 kinase - فسفاتیدیل آنزیم 3 کینازsignal transducers and activators of transcription - مبدل سیگنال و فعال کننده رونویسیGist - مشتاقPartial response - پاسخ جزئیcomplete response - پاسخ کاملPET - پتmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenJAK - چگونهplatelet-derived growth factor receptor - گیرنده عامل فاکتور رشد یافته پلاکت
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
Mutated oncogenic KIT is a therapeutic target in melanoma. We conducted a multicenter phase II trial on the KIT inhibitor nilotinib in patients with unresectable melanoma harboring KIT alteration. The primary endpoint was the response rate (complete response or partial response following Response Evaluation Criteria in Solid Tumors criteria) at 6 months. Pharmacodynamic studies using KIT sequencing, qPCR array, and immunostaining of downstream KIT effectors were performed during treatment. Twenty-five patients were included and received 400 mg oral nilotinib twice daily. At 6 months, nilotinib induced tumor response in four patients. The best overall response rate was 20% and the disease control rate was 56%, limited to patients harboring exon 11 or 13 mutations. Four patients exhibited durable response, including three persisting (3.6 and 2.8 years for two patients with stage IIIC and 2.5 years for one with IVM1b melanoma). A reduction in signal transducer and activator of transcription (STAT) 3 phosphorylation and its effectors (BCL-2, MCL-1) in tumors during follow-up was significantly associated with clinical response. In the KIT-mutated melanoma cell line M230, nilotinib reduced STAT3 signaling and STAT inhibitors were as efficient as KIT inhibitors in reducing cell proliferation. Our study evidences a significant association between STAT3 inhibition and response to nilotinib, and provides a rationale for future research assessing STAT inhibitors in KIT-mutated melanoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 1, January 2018, Pages 58-67
Journal: Journal of Investigative Dermatology - Volume 138, Issue 1, January 2018, Pages 58-67
نویسندگان
Julie Delyon, Sylvie Chevret, Thomas Jouary, Sophie Dalac, Stephane Dalle, Bernard Guillot, Jean-Philippe Arnault, Marie-Françoise Avril, Christophe Bedane, Guido Bens, Anne Pham-Ledard, Sandrine Mansard, Florent Grange, Laurent Machet, Nicolas Meyer,