Memorial Sloan-Kettering Cancer Center, Melanoma-Sarcoma Division, New York, NY 10065, USA.
Cancer J. 2012 Mar-Apr;18(2):137-41. doi: 10.1097/PPO.0b013e31824b2404.
Melanoma is a heterogeneous disease representing distinct biologic and genetic subsets. Activating mutations in KIT have been discovered in a significant proportion of melanomas arising from acral, mucosal, and chronically sun-damaged sites and represent an important melanoma genetic subset. Initially, KIT was believed to function as a tumor suppressor, but additional research suggests that, in certain contexts, KIT functions as an oncogene. Therapeutic strategies targeting KIT with imatinib demonstrated remarkable efficacy in patients with gastrointestinal stromal tumors, but initial trials in melanoma were unsuccessful. Nevertheless, case reports continued to surface that demonstrated the remarkable efficacy of imatinib for patients with specific KIT genetic aberrations. Recently, trials of imatinib have selected patients with KIT genetic aberrations and have shown promising results. Current efforts are investigating additional agents that target KIT and testing KIT inhibitors in combination with other agents to improve the outcome for patients with this genetic subset of melanoma.
黑色素瘤是一种异质性疾病，代表了不同的生物学和遗传学亚群。在肢端、黏膜和慢性日光损伤部位发生的黑色素瘤中，发现了 KIT 的激活突变，这代表了一个重要的黑色素瘤遗传亚群。最初，KIT 被认为是一种肿瘤抑制基因，但进一步的研究表明，在某些情况下，KIT 作为一种致癌基因发挥作用。用伊马替尼靶向 KIT 的治疗策略在胃肠道间质瘤患者中显示出显著的疗效，但在黑色素瘤的初步试验中并不成功。然而，继续出现的病例报告表明，伊马替尼对具有特定 KIT 遗传异常的患者具有显著疗效。最近，伊马替尼的试验选择了具有 KIT 遗传异常的患者，并显示出有希望的结果。目前正在研究针对 KIT 的其他药物，并测试 KIT 抑制剂与其他药物联合使用，以改善这一遗传亚群黑色素瘤患者的预后。
