On the way to targeted therapy of mast cell neoplasms: identification of molecular targets in neoplastic mast cells and evaluation of arising treatment concepts.
On the way to targeted therapy of mast cell neoplasms: identification of molecular targets in neoplastic mast cells and evaluation of arising treatment concepts.
复制标题
肥大细胞肿瘤靶向治疗之路：肥大细胞肿瘤分子靶标的鉴定和新治疗概念的评估。
DOI：
10.1111/j.0960-135x.2004.01369.x
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发表时间：
2004
影响因子：
5.5
通讯作者：
Metcalfe,DD
中科院分区：
文献类型：
--
作者：
Valent,P;Ghannadan,M;Akin,C;Krauth,M-T;Selzer,E;Mayerhofer,M;Sperr,WR;Arock,M;Samorapoompichit,P;Horny,H-P;Metcalfe,DD
几种新兴的骨髓肿瘤治疗概念是基于靶向细胞表面抗原、信号传导通路或关键效应分子的新型药物。系统性肥大细胞增多症是一种造血系统肿瘤，在大多数患者中表现为惰性骨髓增生性疾病，但也可表现为侵袭性疾病，甚至表现为急性白血病。在患有侵袭性疾病或肥大细胞白血病的患者中，在大多数情况下对常规治疗的反应较差，并且预后严重。因此，已经进行了许多尝试来定义针对这些患者的新治疗策略。一个有前途的方法可能是确定新的目标和开发有针对性的药物治疗。在这篇文章中，我们支持肿瘤性肥大细胞确实表达了许多潜在的分子靶点，包括免疫反应性CD抗原，小眼症转录因子（MITF）和Bcl-2家族成员。此外，酪氨酸激酶受体KIT和下游信号通路已被提议作为特定药理学干预的靶点。一个特别的挑战是疾病相关的D816 V突变的KIT变体，它对包括STI 571在内的多种酪氨酸激酶抑制剂具有抗性，但可能对最近开发的靶向化合物敏感。在不久的将来，应在即将进行的临床试验中评价靶向特异性方法在恶性肥大细胞疾病中的治疗潜力。
Several emerging treatment concepts for myeloid neoplasms are based on novel drugs targeting cell surface antigens, signalling pathways, or critical effector molecules. Systemic mastocytosis is a haematopoietic neoplasm that behaves as an indolent myeloproliferative disease in most patients, but can also present as aggressive disease or even as an acute leukaemia. In patients with aggressive disease or mast cell leukaemia, the response to conventional therapy is poor in most cases, and the prognosis is grave. Therefore, a number of attempts have been made to define novel treatment strategies for these patients. One promising approach may be to identify novel targets and to develop targeted drug therapies. In this article, we support the notion that neoplastic mast cells indeed express a number of potential molecular targets including immunoreactive CD antigens, the microphthalmia transcription factor (MITF), and members of the Bcl‐2 family. In addition, the tyrosine kinase receptor KIT and downstream signalling pathways have been proposed as targets of a specific pharmacological intervention. A particular challenge is the disease‐related D816V‐mutated variant of KIT, which is resistant against diverse tyrosine kinase inhibitors including STI571, but may be sensitive to more recently developed targeted compounds. The therapeutic potential of target‐specific approaches in malignant mast cell disorders should be evaluated in forthcoming clinical trials in the near future.