The novel Trk receptor tyrosine-kinase inhibitor CEP-701 (KT-5555) exhibits antitumor efficacy against human pancreatic carcinoma (Panc1) xenograft growth and in vivo invasiveness
The novel Trk receptor tyrosine-kinase inhibitor CEP-701 (KT-5555) exhibits antitumor efficacy against human pancreatic carcinoma (Panc1) xenograft growth and in vivo invasiveness
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DOI：
10.1111/j.1749-6632.1999.tb09530.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Ruggeri, BA
中科院分区：
文献类型：
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作者：
Miknyoczki, SJ;Dionne, CA;Ruggeri, BA
胰腺导管腺癌（PDAC）患者的生存率是所有癌症中最差的，导致这种不良预后的因素是缺乏有效的早期检测、高转移率和对可用治疗方式的一般难治性反应。最常用的治疗方法-化疗和放疗-主要用于缓解症状，手术是唯一的“治愈性”治疗选择。对于局部晚期疾病或手术无法切除的患者，联合使用治疗方式是唯一可用的治疗方法。这些选择仍然不足以：这种癌症的侵袭性行为和不良预后与许多生长因子及其同源受体的表达增加有关，我们以前已经证明了Trk受体的异常表达（Trks A、B和C）和双相，特异性神经营养剂对PDAC细胞体外侵袭力的剂量依赖性反应。基于这些数据，我们已经评估了使用以下抑制神经营养因子-Trk相互作用的治疗潜力：皮下（s.c.）和来自低分化PDAC细胞系Panc 1的气管异种移植物。BID持续21天抑制：Pancl s.c.异种移植物中的肿瘤显著性方式（p
The survival rate for patients with pancreatic ductal adenocarcinoma (PDAC) is among the poorest for all cancers, The factors that contribute to this poor prognosis are lack of effective early detection, high rate of metastases and a generally refractory response to available treatment modalities,The most commonly used treatment methods-chemotherapy and radiation therapy-are mainly used for symptom palliation, with surgery being the only "curative" treatment option. The use of combinations of treatment modalities is the only therapy available to patients with locally advanced disease or that which is surgically unresectable. These options are still not sufficient to: increase patient survival time significantly,The aggressive behavior and poor prognosis of this cancer is associated with an increased expression of many growth factors and their cognate receptors, We have demonstrated previously the aberrant expression of the Trk receptors (Trks A, B, and C) in PDAC specimens and human PDAC-derived cell lines and a biphasic, dose-dependent response of specific neurotrophic agents on the in vitro invasiveness of PDAC cells. Based on these data we have evaluated the therapeutic potential of inhibiting neurotrophin-Trk interactions using:a selective Trk tyrosine kinase inhibitor (CEP-701) on subcutaneous (s.c.) and tracheal xenografts derived from the poorly differentiated PDAC cell line, Panc1.We demonstrate that CEP-701 administration at 10 mg/kg s.c. BID for 21 days inhibited: tumor growth of the Panc1 s.c. xenografts in a statistically-significant manner (p