Alkeraye S, Dadban A, Lok C, Arnault J P, Chaby G
CHRU of Lille, CHRU of Amiens, King Khaled University Hospital.
Dermatol Online J. 2016 Jan 15;22(1):13030/qt13s758x1.
Melanoma is an aggressive tumor with advanced disease characterized by widespread metastatic lesions and the tumor has traditionally 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%. 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. 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. We report a case of non-kit mutated metastatic vaginal melanoma showing impressive response to nilotinib.
黑色素瘤是一种侵袭性肿瘤，晚期疾病以广泛的转移病灶为特征，并且该肿瘤传统上对大多数治疗形式具有抗性。确实，转移性黑色素瘤预后非常差，中位生存时间为8 - 9个月，估计3年生存率低于15%。我们对黑色素瘤细胞基因谱以及驱动恶性转化的分子因素的理解最近取得了进展，这导致了众多新治疗靶点的识别。KIT是具有KIT激活突变的癌症（如胃肠道间质瘤（GIST））中已确立的治疗靶点，并且使用包括甲磺酸伊马替尼在内的各种KIT小分子抑制剂已取得了相当大的疗效。尼罗替尼是配体诱导的PDGFRα和PDFGRβ激酶活性以及携带外显子13或外显子11突变的组成型激活KIT的自磷酸化的抑制剂（IC50值分别为0.2和0.027 μmol/L），其疗效与伊马替尼相当。我们报告了一例非KIT突变的转移性阴道黑色素瘤对尼罗替尼表现出显著反应的病例。
