英国研究人员日前报告说,他们发现一种药物可消除约半数患小细胞肺癌的实验鼠体内的肿瘤。研究人员希望用这种药物有效治疗小细胞肺癌这一致死率极高的恶性癌症。
英国帝国理工学院等机构的研究人员在美国新一期《癌症研究》杂志上报告说,小细胞肺癌患者体内癌细胞扩散速度很快,难以用手术治疗。研究人员发现,一种名为成纤维细胞生长因子2的生长激素在这种癌细胞快速扩散过程中起主要作用,而药物PD173074可阻断这种激素的作用。动物实验表明,这种药物能消除约50%患有小细胞肺癌的实验鼠体内的肿瘤。
研究显示,这种药物还可增强化疗效果。目前化疗是治疗小细胞肺癌的主要手段,但其通常只在最初治疗时有效,肿瘤细胞很快就能适应并重新扩散。动物实验显示,在化疗的同时使用PD173074,可更高效地抑制肿瘤细胞的生长和扩散。
研究人员表示,明年将开展临床试验,希望能在此基础上找到有效治疗小细胞肺癌的方法。
肺癌分为小细胞肺癌和非小细胞肺癌,小细胞肺癌在肺癌中所占比例约为五分之一。(生物谷Bioon.com)
生物谷推荐原始出处:
Cancer Research 69, 8645, November 15, 2009.doi: 10.1158/0008-5472.CAN-09-1576
The Fibroblast Growth Factor Receptor Inhibitor PD173074 Blocks Small Cell Lung Cancer Growth In vitro and In vivo
Olivier E. Pardo1, John Latigo2, Rosemary E. Jeffery3, Emma Nye4, Richard Poulsom3, Bradley Spencer-Dene4, Nick R. Lemoine5, Gordon W. Stamp4, Eric O. Aboagye2 and Michael J. Seckl1
1 Lung Cancer Biology Group, Cancer Research UK Laboratories and 2 Molecular Therapy Group, Clinical Sciences Centre, Hammersmith Hospital Campus of Imperial College London; 3 In Situ Hybridisation and 4 Experimental Pathology Laboratories, Cancer Research UK London Research Institute; and 5 Institute of Cancer, Barts and The London, School of Medicine and Dentistry, London, United Kingdom
Lung cancer is the commonest cancer killer. Small cell lung cancer (SCLC) is initially chemosensitive, but rapidly relapses in a chemoresistant form with an overall survival of <5%. Consequently, novel therapies are urgently required and will likely arise from an improved understanding of the disease biology. Our previous work showed that fibroblast growth factor-2 induces proliferation and chemoresistance in SCLC cells. Here, we show that the selective fibroblast growth factor receptor (FGFR) inhibitor PD173074 blocks H-510 and H-69 SCLC proliferation and clonogenic growth in a dose-dependent fashion and prevents FGF-2–induced chemoresistance. These effects correlate with the inhibition of both FGFR1 and FGFR2 transphosphorylation. We then determined the efficacy of daily oral administration of PD173074 for 28 days in two human SCLC models. In the H-510 xenograft, tumor growth was impaired similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham–treated animals. Crucially, the effect of cisplatin was significantly potentiated by coadministration of PD173074. More dramatically, in H-69 xenografts, PD173074 induced complete responses lasting >6 months in 50% of mice. These effects were not a consequence of disrupted tumor vasculature but instead correlated with increased apoptosis (caspase 3 and cytokeratin 18 cleavage) in excised tumors. Moreover, in vivo imaging with 3'-deoxy-3'-[18F]fluorothymidine–positron emission tomography ([18F]FLT-PET) showed decreased intratumoral proliferation in live animals treated with the compound at 7 to 14 days. Our results suggest that clinical trials of FGFR inhibitors should be undertaken in patients with SCLC and that [18F]FLT-PET imaging could provide early in vivo evidence of response.