Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells
Autor: | Simran Venkatraman, Kanokpan Wongprasert, Kiren Yacqub-Usman, Brinda Balasubramanian, Isioma U. Egbuniwe, Supeecha Kumkate, Rutaiwan Tohtong, Noppadol Larbcharoensub, Thannicha Sae-Lao, Abhik Mukherjee, Chinnawut Suriyonplengsaeng, David O. Bates, Boonyakorn Boonsri, Dhanwant Gomez, Abed M. Zaitoun, Tavan Janvilisri, Thiti Kuakpaetoon, Pakpoom Thintharua, Pam Collier, Anna M. Grabowska, Kyaw Zwar Myint |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Receptor expression Afatinib information science Cholangiocarcinoma 03 medical and health sciences ErbB Receptors 0302 clinical medicine ErbB Gastrointestinal Cancer Antineoplastic agents parasitic diseases medicine Humans cardiovascular diseases Epidermal growth factor receptor Protein Kinase Inhibitors biology Cytotoxins business.industry ErbB receptors fungi ErbB targeted drugs Cell cycle Gemcitabine 030104 developmental biology Oncology 030220 oncology & carcinogenesis cardiovascular system Cancer research biology.protein Original Article Erlotinib business medicine.drug |
Zdroj: | Cancer Research and Treatment : Official Journal of Korean Cancer Association |
ISSN: | 2005-9256 1598-2998 |
Popis: | 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. |
Databáze: | OpenAIRE |
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