封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 27 郭珩輝教授主要研究癌症蛋白生物標記物和天然藥物開發，包括用來治療癌症的抗體和以基於毒液 的肽作為藥物的靶向治療。在設於劍橋大學的英國癌症研究院劍橋中心兼任訪問科學家。學術期刊 《Biomolecules》和《Toxins》的編輯委員會成員及客座主編，《Frontiers in Molecular Bioscience》 副主編。 Prof Henry Kwok Hang Fai’s research interests cover cancer biomarkers discovery and natural drug development, including antibody and venom-based peptide targeted therapy for cancer treatment. He also serves as a visiting scientist at the Cancer Research UK Cambridge Institute, University of Cambridge. He is an editorial board member and guest editor of both Biomolecules and Toxins, and associate editor of Frontiers in Molecular Biosciences. 抑制性抗體的結構 The structure of the inhibitory antibody 近年不少醫學報告指出，很多非小細胞 肺癌使用酪氨酸激酶抑制劑後，不久就 會產生抗藥性。雖然轉用新一代藥物有 可能消除這個問題，但病人經過幾次療 程後，有可能又對新藥產生抗藥性。郭 教授說：「這個過程有機會不斷重複， 一直轉換藥物往往不利治療。」 為了打破困局，郭教授的團隊開發了抑 制性抗體「A9(B8)IgG」，以腫瘤壞死 因子──α轉化酶（TACE/ADAM17） 作為標靶。郭教授說：「我們的研究顯 示，這種抗體與酪氨酸激酶抑制劑結合 使用，能夠增強抑制劑的效力，克服 EGFR突變引致的抗藥性。」憑著這項 發現，郭教授與健康科學學院助理教授 謝瑞瑜正在為這款新型抗體及其開發申 請一項美國專利，有助他們爭取藥廠和 澳門科學技術發展基金支持。 在澳門科學技術發展基金資助下，郭教 授的團隊與健康科學學院副教授譚建業 正在透過進一步的動物實驗，展開前期 臨床研究。他們也準備與澳門鏡湖醫院 病理科顧問醫生陳建勇合作，取得本地 病人的癌組織和細胞，用來深入研究抗 體的效用，並找出最佳的聯合用藥策略。 In recent years, many medical reports have shown that many NSCLC patients can develop resistance to EGFR tyrosine kinase inhibitors in a relatively short period of treatment. Although this problem might be mitigated by changing to the next generation of new drug treatment, patients can still develop resistance to the new drug after several rounds of treatment. ‘This process can go on and on, and shifting from drug to drug often hampers the treatment,’ says Prof Kwok. To break this cycle, Prof Kwok’s team developed a new inhibitory antibody named A9(B8) IgG, which targets Tumour Necrosis Factor‑α Converting Enzyme (TACE/ADAM17) . ‘Our research suggests that this antibody, when used in combination with EGFR‑TKI, can potentiate the anticancer effects of EGFR‑TKI and overcome drug resistance due to EGFR mutations.’ Prof Kwok and FHS Assistant Professor Xie Ruiyu have filed a US patent application for this antibody and its development, which helped them obtain support from some pharmaceutical companies and the Macao Science and Technology Development Fund (FDCT, in its Portuguese acronym). With funding support from FDCT, Prof Kwok’s team and FHS Associate Professor Tam Kin Yip have been carrying out animal experimentation to conduct pre-clinical trial studies. They are also preparing to cooperate with Consultant Pathologist Dr Chan Kin Iong at the Kiang Wu Hospital in Macao to obtain cancer tissues and cells from local patients, in order to study the antibody’s effectiveness, and to find out the best drug combination strategies.
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