Lim Jin Hong Park, Keun wan Choi Kyung Hwa Kim Chan Wung Lee Jae Ha Weicker Raymond PAN, CHEOL HO Kim Seok-Mo Park Ki Cheong 2024-01-12T03:01:31Z 2024-01-12T03:01:31Z 2022-08-09 2022-07 1661-6596 https://pubs.kist.re.kr/handle/201004/76665 Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells. English Multidisciplinary Digital Publishing Institute (MDPI) Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma Article 10.3390/ijms23147971 1 International Journal of Molecular Sciences, v.23, no.14 International Journal of Molecular Sciences 23 14 Y scie scopus 000833696100001 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article CA2+ HOMEOSTASIS OVARIAN-CANCER CALCIUM PUMPS APOPTOSIS RESISTANCE SERCA CHEMOTHERAPY MITOCHONDRIA NEOADJUVANT STRESS candidate 19 candidate 23 cancer stem cells patient-derived anti-cancer drug-resistant hepatocellular carcinoma endoplasmic reticulum stress sarcoplasmic endoplasmic reticulum calcium ATPase thapsigargin