Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer

作者：Yuna Kim, Hyeok Jun Yun, Kyung Hwa Choi, Chan Wung Kim, Jae Ha Lee, Raymond Weicker, Seok‐Mo Kim, Ki Cheong Park · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms242216413 · 被引用次数：11 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Cancer-related Molecular Pathways、Cancer Mechanisms and Therapy

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.