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C-Kit non-mutated metastatic melanoma showing positive response to Nilotinib

机译:C-Kit非突变转移性黑色素瘤对尼洛替尼呈阳性反应

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摘要

Melanoma is an aggressive tumor with advanced disease characterized by widespread metastatic?lesions and the tumor hastraditionally been resistant to most forms of treatment. Indeed, metastatic melanoma has a very?poor prognosis with a median survival time of 8–9 months and an estimated 3-year survival rate of?less than 15 % [1].Recent advances in our understanding of the genetic profile of melanoma cells and the molecular?factors that drive malignant transformation have resulted in the identification of numerous new?therapeutic targets.KIT is an established therapeutic target in cancers with activating mutations of KIT, such as?gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various?small molecule inhibitors of KIT including imatinib mesylate [2].Nilotinib is an inhibitor of ligand-induced PDGFRα and PDFGRβ kinase activity and?autophosphorylation of constitutively activated KIT harboring exon 13 or exon 11 mutations (IC50?values of 0.2 and 0.027 μmol/L, respectively), with efficacy comparable to that of imatinib [2].We report a case of non-kit mutated metastatic vaginal melanoma showing impressive response to?nilotinib.
机译:黑色素瘤是一种具有进展性疾病的侵袭性肿瘤,其特征在于广泛的转移性病变,并且该肿瘤传统上已对大多数治疗形式产生抗性。的确,转移性黑素瘤的预后很差,中位生存时间为8–9个月,估计3年生存率不到15%[1]。我们对黑素瘤细胞的遗传学认识的最新进展KIT是具有KIT激活突变的癌症(例如胃肠道间质瘤(GIST))中已确立的治疗靶标,并且已经有相当大的疗效。 Nilotinib是配体诱导的PDGFRα和PDFGRβ激酶活性以及具有第13外显子或第11外显子突变的组成型激活KIT的自磷酸化的抑制剂(IC50的值分别为0.2和1。分别为0.027μmol/ L),疗效与伊马替尼[2]相当。我们报道了一例非试剂盒突变的转移性阴道黑素瘤对尼罗替尼有令人印象深刻的反应笔尖。

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