中國醫藥大學校長洪明奇院士帶領國際合作團隊,研究成果榮登國際知名期刊《肝病學雜誌》

【記者 玉女 台中 報導】

世界知名期刊《肝病學雜誌》發表最新醫學研究成果;台灣中國醫藥大學校長洪明奇院士帶領的國際合作團隊,首次發現了孤兒受體ROS1蛋白RNase7在肝癌治療中所具有的關鍵作用,提供肝癌標靶治療的新策略,有助於患者提高生存期。

中國醫藥大學洪明奇校長研究團隊與美國德州大學安德森癌症中心和復旦大學附屬中山醫院合作團隊研究成果,發表名為「探討Ribonuclease 7驅動之ROS1活化作為肝細胞癌的潛在治療標靶」“Ribonuclease 7-driven activation of ROS1 is a potential therapeutic target in hepatocellular carcinoma”之研究論文,於10月4日刊登世界知名期刊《肝病學雜誌》,受到醫學界的高度重視。

肝細胞癌(HCC)是原發性肝癌的最主要形式,為全球死亡率第二高的癌症;雖然目前有多種小分子多激酶抑製劑已獲美國食品藥物管理局(US Food and Drug Administration)批准用於肝細胞癌的一線或二線治療。可是,這些現有的藥物僅能提高患者約幾個月的生存時間,總體反應率尚不到20%。因此,為肝細胞癌患者尋求有效的生物標記和新的替代療法是當前急待解決的臨床需求。

國際知名癌症基因科學家洪明奇校長表示,受體酪胺酸激酶(receptor tyrosine kinase,RTK)在細胞分化、增殖、遷移以及血管生成等過程中具有關鍵調節作用,RTK訊號之失調將導致多種癌症的發展。而ROS1是RTK家族中最後一個具有激酶活性的孤兒受體。ROS1雖然已被發現超過30年,但由於其配體始終未知,故在細胞調節和疾病發展中之功能尚不清楚。

為此,洪明奇校長帶領國際合作團隊研究通過篩選多種Ribonuclease (RNase)家族蛋白,發現RNase7特異結合於ROS1胞外區N3-P2域,RNase7刺激可導致ROS1的末端酪胺酸殘基2274位點(Y2274)磷酸化,進而活化ROS1之訊息傳導路徑。

研究團隊通過建立小鼠原位肝癌模型以及HCC患者異種移植模型發現,抑制RNase7誘導的ROS1活化將可大大減緩腫瘤的生長並延長荷瘤小鼠的生存期;通過ROS1抑製劑crizotinib治療後的小鼠,其腫瘤細胞中的ROS1磷酸化和ERK1/2磷酸化水平明顯降低,肝癌肺轉移腫瘤數量顯著減少。

洪明奇校長國際研究團隊進一步檢測並分析了260例肝細胞癌患者樣本中之ROS1和RNase7表現量以及其臨床數據,發現具ROS1/RNase7高表現的患者往往具有較差的總體生存時間,並且更容易有復發之情形,這類患者將有望能夠通過接受ROS1抑制劑的治療獲益以提高生存期。

這項研究首次發現了孤兒受體ROS1的配體,揭示了RNase7所驅動之ROS1路徑活化對腫瘤細胞生長的功能。此外,RNase7更有潛力開發為對HCC病人進行以ROS1標靶治療的血液生物標記,將可為臨床治療策略之選擇提供了重要的參考依據。

111 thoughts on “中國醫藥大學校長洪明奇院士帶領國際合作團隊,研究成果榮登國際知名期刊《肝病學雜誌》

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