Publication: Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells
Issued Date
2021-04-01
Resource Type
ISSN
20059256
15982998
15982998
Other identifier(s)
2-s2.0-85104369484
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Mahidol University
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SCOPUS
Bibliographic Citation
Cancer Research and Treatment. Vol.53, No.2 (2021), 457-470
Suggested Citation
Boonyakorn Boonsri, Kiren Yacqub-Usman, Pakpoom Thintharua, Kyaw Zwar Myint, Thannicha Sae-Lao, Pam Collier, Chinnawut Suriyonplengsaeng, Noppadol Larbcharoensub, Brinda Balasubramanian, Simran Venkatraman, Isioma U. Egbuniwe, Dhanwant Gomez, Abhik Mukherjee, Supeecha Kumkate, Tavan Janvilisri, Abed M. Zaitoun, Thiti Kuakpaetoon, Rutaiwan Tohtong, Anna M. Grabowska, David O. Bates, Kanokpan Wongprasert Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells. Cancer Research and Treatment. Vol.53, No.2 (2021), 457-470. doi:10.4143/CRT.2020.585 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/76223
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Title
Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells
Author(s)
Boonyakorn Boonsri
Kiren Yacqub-Usman
Pakpoom Thintharua
Kyaw Zwar Myint
Thannicha Sae-Lao
Pam Collier
Chinnawut Suriyonplengsaeng
Noppadol Larbcharoensub
Brinda Balasubramanian
Simran Venkatraman
Isioma U. Egbuniwe
Dhanwant Gomez
Abhik Mukherjee
Supeecha Kumkate
Tavan Janvilisri
Abed M. Zaitoun
Thiti Kuakpaetoon
Rutaiwan Tohtong
Anna M. Grabowska
David O. Bates
Kanokpan Wongprasert
Kiren Yacqub-Usman
Pakpoom Thintharua
Kyaw Zwar Myint
Thannicha Sae-Lao
Pam Collier
Chinnawut Suriyonplengsaeng
Noppadol Larbcharoensub
Brinda Balasubramanian
Simran Venkatraman
Isioma U. Egbuniwe
Dhanwant Gomez
Abhik Mukherjee
Supeecha Kumkate
Tavan Janvilisri
Abed M. Zaitoun
Thiti Kuakpaetoon
Rutaiwan Tohtong
Anna M. Grabowska
David O. Bates
Kanokpan Wongprasert
Abstract
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.