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논문 기본 정보

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Boonyakorn Boonsri (Faculty of Science Mahidol University Bangkok Thailand) Kiren Yacqub-Usman (Biodiscovery Institute University of Nottingham Nottingham UK) Pakpoom Thintharua (Faculty of Science Mahidol University Bangkok Thailand) Kyaw Zwar Myint (Mahidol University Bangkok Thailand) Thannicha Sae-Lao (Siam University Bangkok Thailand) Pam Collier (Biodiscovery Institute University of Nottingham Nottingham UK) Chinnawut Suriyonplengsaeng (Faculty of Science Mahidol University Bangkok Thailand) Noppadol Larbcharoensub (Mahidol University Bangkok Thailand) Brinda Balasubramanian (Mahidol University Bangkok Thailand) Simran Venkatraman (Mahidol University Bangkok Thailand) Isioma U. Egbuniwe (Biodiscovery Institute University of Nottingham Nottingham UK) Dhanwant Gomez (University of Nottingham Nottingham UK) Abhik Mukherjee (Biodiscovery Institute University of Nottingham Nottingham UK) Supeecha Kumkate (Mahidol University Bangkok Thailand) Tavan Janvilisri (Mahidol University Bangkok Thailand) Abed M Zaitoun (Nottingham University Hospitals NHS Trust Nottingham Thailand) Thiti Kuakpaetoon (Rajavithi Hospital Bangkok Thailand) Rutaiwan Tohtong (Mahidol University Bangkok Thailand) Anna M Grabowska (Biodiscovery Institute University of Nottingham Nottingham UK) David O. Bates (Biodiscovery Institute University of Nottingham Nottingham UK) Kanokpan Wongprasert (Faculty of Science Mahidol University Bangkok Thailand)
저널정보
대한암학회 Cancer Research and Treatment Cancer Research and Treatment 제53권 제2호
발행연도
2021.1
수록면
457 - 470 (14page)

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Purpose The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells. Materials and Methods ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments. Results CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib. Conclusion Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.
#Cholangiocarcinoma #ErbB receptors #ErbB targeted drugs #Antineoplastic agents #Gemcitabine #Afatinib

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참고문헌 (33)

참고문헌 신청
Konfortion J / 2014 / Coverage of common cancer types in UK national newspapers : a content analysis / BMJ Open 4:e004677 google schola Maroni L / 2013 / The significance of genetics for cholangiocarcinoma development / Ann Transl Med 1:28 google schola Sahu S / 2017 / Targeted therapy in biliary tract cancers-current limitations and potentials in the future / J Gastrointest Oncol 8:324~336 google schola 형재원 / 2019 / Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin / Cancer Research and Treatment 51(3):901~909 dbpia Ritter CA / 2003 / The epidermal growth factor receptor-tyrosine kinase : a promising therapeutic target in solid tumors / Semin Oncol 30(1 Suppl 1):3~11 google schola

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