美國加州大學(xué)圣地亞哥分校醫(yī)學(xué)院和穆爾斯癌癥中心的研究人員發(fā)現(xiàn)一種新的生物標(biāo)志物和胰腺癌的治療靶標(biāo)。相關(guān)論文發(fā)表在5月15日的Cancer Research雜志上,。
胰腺癌是引發(fā)癌癥相關(guān)死亡的第四大原因,，初診患者的平均存活時(shí)間不到一年，只有3％至5％的患者有5年生存率,。因此,，迫切需要的生物標(biāo)志物來識別胰腺癌發(fā)病的初期，這一標(biāo)志物可能也是可行的藥物靶標(biāo),。
加州大學(xué)圣迭戈分校病理學(xué)和穆爾斯癌癥中心博士后研究人員,，文章第一作者Jonathan Kelber博士說：我們發(fā)現(xiàn)，激酶PEAK1在胰腺癌早期就被打開,。 這種蛋白質(zhì)在患者的腫瘤切片中很容易被檢測出來,。
PEAK1是一種酪氨酸激酶，在許多細(xì)胞功能中起到“開”或“關(guān)閉”作用,。胰腺癌患者PEAK1表達(dá)的增加,，催化胰腺癌腫瘤細(xì)胞增殖，使得PEAK1作為一種生物標(biāo)志物和小分子藥物治療的靶點(diǎn),。
此外胰腺癌進(jìn)展期間PEAK1的水平也增加，科學(xué)家們發(fā)現(xiàn)PEAK1肺腫瘤的生長和轉(zhuǎn)移是必要的,。
Kelber說：PEAK1是一個(gè)重要的信號樞紐,，能調(diào)節(jié)細(xì)胞遷移和增殖。我們發(fā)現(xiàn)如果你把它敲除,，腫瘤在臨床前小鼠模型中的形成會很小,，也未能有效轉(zhuǎn)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.
