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Anti-Cancer SERCA Inhibitors Targeting Sorafenib-Resistant Human Papillary Thyroid Carcinoma

Authors
 Hang-Seok Chang  ;  Yonjung Kim  ;  So Young Lee  ;  Hyeok Jun Yun  ;  Ho-Jin Chang  ;  Ki Cheong Park 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.24(8) : 7069, 2023-04 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2023-04
MeSH
Animals ; Antineoplastic Agents* / pharmacology ; Antineoplastic Agents* / therapeutic use ; Disease Models, Animal ; Endoplasmic Reticulum ; Humans ; Sorafenib / pharmacology ; Sorafenib / therapeutic use ; Thyroid Cancer, Papillary / drug therapy ; Thyroid Neoplasms* / drug therapy ; Thyroid Neoplasms* / genetics ; Thyroid Neoplasms* / pathology
Keywords
anti-cancer drug-resistant papillary thyroid cancer ; human papillary thyroid cancer ; sorafenib
Abstract
Thyroid cancer is generally curable and, in many cases, can be completely treated, although it can sometimes recur after cancer therapy. Papillary thyroid cancer (PTC) is known as one of the most general subtypes of thyroid cancer, which take up nearly 80% of whole thyroid cancer. However, PTC may develop anti-cancer drug resistance via metastasis or recurrence, making it practically incurable. In this study, we propose a clinical approach that identifies novel candidates based on target identification and validation of numerous survival-involved genes in human sorafenib-sensitive and -resistant PTC. Consequently, we recognized a sarco/endoplasmic reticulum calcium ATPase (SERCA) in human sorafenib-resistant PTC cells. Based on the present results, we detected novel SERCA inhibitor candidates 24 and 31 via virtual screening. These SERCA inhibitors showed remarkable tumor shrinkage in the sorafenib-resistant human PTC xenograft tumor model. These consequences would be clinically worthwhile for the development of a new combinatorial strategy that effectively targets incredibly refractory cancer cells, such as cancer stem cells and anti-cancer drug-resistant cells.
Files in This Item:
T202303015.pdf Download
DOI
10.3390/ijms24087069
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
Yun, Hyeok Jun(윤혁준) ORCID logo https://orcid.org/0000-0001-6004-0782
Chang, Hang Seok(장항석) ORCID logo https://orcid.org/0000-0002-5162-103X
Chang, Ho Jin(장호진) ORCID logo https://orcid.org/0000-0002-8940-3484
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195371
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