打开APP

Clin Cancer Res:可阻断癌症生长关键信号的抗癌新药

  1. pictilisib
  2. 一期临床
  3. 抗癌药
  4. 癌症
  5. 耐药性

来源:生物谷 2014-12-24 19:06

2014年12月24日讯 /生物谷BIOON/ --一个实验性抗癌药物可阻断对癌细胞存活,生长和扩散重要的“驱动力”。一种实验性药物pictilisib的一期临床试验,发现对于癌症患者的安全性是可控,实验剂量药物能成功地阻止PI3激

2014年12月24日讯 /生物谷BIOON/ --一个实验性抗癌药物可阻断对癌细胞存活,生长和扩散重要的“驱动力”。一种实验性药物pictilisib的一期临床试验,发现对于癌症患者的安全性是可控,实验剂量药物能成功地阻止PI3激酶途径。

The Institute of Cancer Research研究人员带领完成的这项研究已经扫清了药物pictilisib开展到大规模临床试验的障碍。试验中使用最先进的分子生物学技术来跟踪pictilisib对其靶蛋白分子的活性,显示pictilisib能阻断癌细胞生存,生长和耐药性的重要驱动因子。

这项研究发表在Clinical Cancer Research杂志上。PI3K途径在很多癌症中发挥关键作用,帮助细胞生长失控生长并扩散到身体的其他部位,维持癌细胞存活,并帮助他们抗拒治疗。ICR与Piramed制药合作发现PI3K抑制剂pictilisib,在试验中,研究人员检测了60例乳腺癌,肠癌,卵巢癌和其他癌症类型患者的血液和肿瘤样本,来测定表征PI3K活性的化学标记物,并监测治疗患者产生的不利影响。在这项研究中患者Pictilisib耐受性良好,只有少数与临床相关剂量的一些严重反应(与治疗相关的事件包括恶心,腹泻和皮疹)。药物被施用后,血液样品PI3K活性的生物标记物下降了90%。

研究人员发现,pictilisib显示的抗肿瘤活性令人鼓舞,在三名肿瘤患者(三种不同类型)中有治疗成效。卵巢癌女性患者治疗后疾病无进展期为四个月,转移性黑色素瘤患者接受治疗9.5个月后疾病得到改善,软组织肉瘤患者接受治疗后疾病保持稳定7.5个月。研究已经表明,pictilisib似乎是阻断患者PI3K,我们相信,通过阻断PI3K,pictilisib能有效对抗多种肿瘤类型。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。谢谢!

First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan–Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors

Debashis Sarker,et al.

Purpose: This first-in-human dose-escalation trial evaluated the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and preliminary clinical activity of pictilisib (GDC-0941), an oral, potent, and selective inhibitor of the class I phosphatidylinositol-3-kinases (PI3K).

Patients and Methods: Sixty patients with solid tumors received pictilisib at 14 dose levels from 15 to 450 mg once-daily, initially on days 1 to 21 every 28 days and later, using continuous dosing for selected dose levels. Pharmacodynamic studies incorporated 18F-FDG-PET, and assessment of phosphorylated AKT and S6 ribosomal protein in platelet-rich plasma (PRP) and tumor tissue.

Results: Pictilisib was well tolerated. The most common toxicities were grade 1–2 nausea, rash, and fatigue, whereas the DLT was grade 3 maculopapular rash (450 mg, 2 of 3 patients; 330 mg, 1 of 7 patients). The pharmacokinetic profile was dose-proportional and supported once-daily dosing. Levels of phosphorylated serine-473 AKT were suppressed >90% in PRP at 3 hours after dose at the MTD and in tumor at pictilisib doses associated with AUC >20 h·μmol/L. Significant increase in plasma insulin and glucose levels, and >25% decrease in 18F-FDG uptake by PET in 7 of 32 evaluable patients confirmed target modulation. A patient with V600E BRAF–mutant melanoma and another with platinum-refractory epithelial ovarian cancer exhibiting PTEN loss and PIK3CA amplification demonstrated partial response by RECIST and GCIG-CA125 criteria, respectively.

Conclusion: Pictilisib was safely administered with a dose-proportional pharmacokinetic profile, on-target pharmacodynamic activity at dose levels ≥100 mg and signs of antitumor activity. The recommended phase II dose was continuous dosing at 330 mg once-daily.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->