靶向药物伊马替尼治疗隆突性皮肤纤维肉瘤的进展

Progress in the treatment of dermatofibrosarcoma protuberans with the targeted drug imatinib

隆突性皮肤纤维肉瘤(dermatofibrosarcoma protuberan,DFSP)是一种局部侵袭性肉瘤,好发于青年至中年人群。通常发生于躯干及四肢近端,也可发生在头颈部。通常表现为缓慢生长的结节或斑块,治疗首选手术切除,但局部复发率高。然而,由于90%的DFSP患者出现17号及22号染色体异位,产生融合基因血小板衍化生长因子B(platelet-derived growth factor B,PDGEB)与其受体(platelet-derived growth factor receptor-β,PDGFR-β)结合,从而激活下游信号传导通路。这一特点既可作为主要发病机制,也是靶向治疗的理论基础。该文对DFSP发病机制、主要靶向药物伊马替尼治疗及伊马替尼产生的原发和继发耐药后潜在的新靶向药物治疗方法进行综述。

Dermatofibrosarcoma protuberans(DFSP)is a locally invasive sarcoma that predisposes to young to middle-aged people,usually occurs in the trunk and proximal extremities,but also in the head and neck.It usually presents as a slow growing nodule or plaque associated with local invasion,surgical excision is the main treatment,but the local recurrence rate is high.Ninety percent of DFSP patients have 17 and 22 chromosome translocation,produces fusion gene COL1A1-PDGFB,that lead to autocrine stimulation of plateletderived growth factor B(PDGFB),then PDGF combines to its receptor platelet-derived growth factor receptor-β(PDGFR-β)and activates downstream signaling,in which way leading to tumor proliferation.The characteristic above mentioned is not only the main pathogenesis of DFSP,but also the theoretical basis of targeted therapy.This article reviews the pathogenesis of DFSP,the targeted treatment of imatinib,and the potential new targeted drug therapy after primary and secondary resistance to imatinib.