Molecular Pharmacology Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Cancer Biol Ther. 2010 Jul 1;10(1):38-43. doi: 10.4161/cbt.10.1.11993. Epub 2010 Jul 9.
Focal adhesion kinase (FAK) is essential in regulating integrin signaling pathways responsible for cell survival and proliferation, as well as motility, making FAK a distinctive target in the field of anticancer drug development, especially with regards to metastatic disease.(1) Our objective was to demonstrate tumor growth inhibition by PF-562,271, a selective inhibitor of FAK and FAK2, or Pyk2,(2) in mouse xenograft models, both subcutaneous and metastatic, employing the human prostate cancer cell line PC3M-luc-C6, a modified PC3M cell line that expresses luciferase. After 2 weeks of treatment with PF-562,271, 25 mg/kg PO BID 5x/wk, the subcutaneous model showed a 62% tumor growth inhibition compared to control based on tumor measurements (p < 0.05), with a 88% vs. a 490% increase in bioluminescent signal for treatment and control respectively (p < 0.05). In the metastasis model, the percent change from baseline, after 18 days of treatment, of the treatment group was 2,854 vs. 14,190% for the vehicle (p < 0.01). These results show that PF-562,271 has a potent effect on metastatic prostate cancer growth in vivo.
黏着斑激酶（FAK）在调节整合素信号通路中起着至关重要的作用，这些信号通路负责细胞的存活和增殖，以及运动性，使 FAK 成为癌症药物开发领域的一个独特靶点，特别是在转移性疾病方面。（1）我们的目的是证明 PF-562,271（FAK 和 FAK2 的选择性抑制剂或 Pyk2）（2）在皮下和转移性的小鼠异种移植模型中，通过表达荧光素酶的人前列腺癌细胞系 PC3M-luc-C6（经改良的 PC3M 细胞系）抑制肿瘤生长。在接受 PF-562,271 治疗 2 周后，25 mg/kg PO BID 5x/wk，与对照组相比，皮下模型的肿瘤生长抑制率为 62%（基于肿瘤测量，p<0.05），治疗组和对照组的生物发光信号分别增加了 88%和 490%（p<0.05）。在转移模型中，治疗组从基线的百分比变化在治疗 18 天后为 2,854%，而载体组为 14,190%（p<0.01）。这些结果表明，PF-562,271 对体内转移性前列腺癌的生长具有很强的作用。
