美国加州大学圣地亚哥分校医学院和穆尔斯癌症中心的研究人员发现一种新的生物标志物和胰腺癌的治疗靶标。相关论文发表在5月15日的Cancer Research杂志上。
胰腺癌是引发癌症相关死亡的第四大原因，初诊患者的平均存活时间不到一年，只有3％至5％的患者有5年生存率。因此，迫切需要的生物标志物来识别胰腺癌发病的初期，这一标志物可能也是可行的药物靶标。
加州大学圣迭戈分校病理学和穆尔斯癌症中心博士后研究人员，文章第一作者Jonathan Kelber博士说：我们发现，激酶PEAK1在胰腺癌早期就被打开。 这种蛋白质在患者的肿瘤切片中很容易被检测出来。
PEAK1是一种酪氨酸激酶，在许多细胞功能中起到“开”或“关闭”作用。胰腺癌患者PEAK1表达的增加，催化胰腺癌肿瘤细胞增殖，使得PEAK1作为一种生物标志物和小分子药物治疗的靶点。
此外胰腺癌进展期间PEAK1的水平也增加，科学家们发现PEAK1肺肿瘤的生长和转移是必要的。
Kelber说：PEAK1是一个重要的信号枢纽，能调节细胞迁移和增殖。我们发现如果你把它敲除，肿瘤在临床前小鼠模型中的形成会很小，也未能有效转移。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3552
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KRas Induces a Src/PEAK1/ErbB2 Kinase Amplification Loop That Drives Metastatic Growth and Therapy Resistance in Pancreatic Cancer
Jonathan A. Kelber, Theresa Reno, Sharmeela Kaushal, Cristina Metildi, Tracy Wright, et al.
Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including human PDACs and pancreatic intraepithelial neoplasia (PanIN). Oncogenic KRas induced a PEAK1-dependent kinase amplification loop between Src, PEAK1, and ErbB2 to drive PDAC tumor growth and metastasis in vivo. Surprisingly, blockade of ErbB2 expression increased Src-dependent PEAK1 expression, PEAK1-dependent Src activation, and tumor growth in vivo, suggesting a mechanism for the observed resistance of patients with PDACs to therapeutic intervention. Importantly, PEAK1 inactivation sensitized PDAC cells to trastuzumab and gemcitabine therapy. Our findings, therefore, suggest that PEAK1 is a novel biomarker, critical signaling hub, and new therapeutic target in PDACs.
