Article
Pharmacology & Pharmacy
Dehua Yu, Simin Qi, Xiaoqing Guan, Wenkai Yu, Xuefei Yu, Maohua Cai, Qinglin Li, Weiyi Wang, Weidong Zhang, Jiang-Jiang Qin
Summary: In this study, the marine-derived natural product terphenyllin was identified to directly interact with STAT3 and exhibit potent anticancer efficacy against gastric cancer through inhibiting the STAT3 signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Mengyuan Liu, Heming Li, Huijing Zhang, Huan Zhou, Taiwei Jiao, Mingliang Feng, Fangjian Na, Mingjun Sun, Mingfang Zhao, Lei Xue, Lu Xu
Summary: By analyzing high-throughput sequencing datasets, this study identified RBMS1 as a potential promoter gene for gastric cancer metastasis, which activates the JAK2/STAT3 signaling pathway and IL-6 transcriptional activation, promoting cell migration and invasion.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Shumin Ouyang, Huaxuan Li, Linlin Lou, Qiuyao Huang, Zhenhua Zhang, Jianshan Mo, Min Li, Jiaye Lu, Kai Zhu, Yunjie Chu, Wen Ding, Jianzheng Zhu, Ziyou Lin, Lin Zhong, Junjian Wang, Peibin Yue, James Turkson, Peiqing Liu, Yuanxiang Wang, Xiaolei Zhang
Summary: Inhibition of STAT3 can trigger ferroptosis and provide a new therapeutic strategy for gastric cancer and chemotherapy resistance. STAT3 negatively regulates the FNR associated genes and establishes a negative STAT3-ferroptosis regulatory axis in gastric cancer. A selective STAT3 inhibitor, W1131, shows significant anti-tumor effects in gastric cancer models by inducing ferroptosis and restores sensitivity to chemotherapy.
Article
Oncology
Ying Bai, Xuye Wang, Mengsi Cai, Chunbo Ma, Youqun Xiang, Wanle Hu, Bin Zhou, Chengguang Zhao, Xuanxuan Dai, Xiaokun Li, Haiyang Zhao
Summary: Cinobufagin, a natural product extracted from toad venom, exhibits high antitumor activity by inhibiting proliferation, migration, invasion, and promoting apoptosis of colorectal cancer cells in vitro and in vivo. The underlying mechanism involves suppression of the STAT3 pathway, leading to inhibition of epithelial-mesenchymal transition.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Qizhi Liu, Stacey Chung, Michael M. Murata, Bingchen Han, Bowen Gao, Maoqi Zhang, Tian-Yu Lee, Evgeny Chirshev, Juli Unternaehrer, Hisashi Tanaka, Armando E. Giuliano, Yukun Cui, Xiaojiang Cui
Summary: Two distinct and diverging cancer cell responses to TOP1 inhibitors were observed in TNBC, with one group being sensitive and the other resistant. The activation patterns of ATR/Chk1 and JNK, as well as the expression of MYC, may serve as predictive markers for cancer cell response to TOP1 inhibitors. The constitutive elevation of MYC expression mediated by JNK activation may represent a novel mechanism governing cancer cell sensitivity to TOP1-targeting therapy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Kavya Ramkumar, Azusa Tanimoto, Carminia M. Della Corte, C. Allison Stewart, Qi Wang, Li Shen, Robert J. Cardnell, Jing Wang, Urszula M. Polanska, Courtney Andersen, Jamal Saeh, J. Elizabeth Pease, Jon Travers, Giulia Fabbri, Carl M. Gay, Jelena Urosevic, Lauren A. Byers
Summary: This study aims to develop therapeutic strategies and biomarkers of response for small cell lung cancer (SCLC). The researchers found that AURKB inhibitor showed promising therapeutic efficacy in SCLC, and high expression of BCL2 predicted resistance to the inhibitor. Therefore, targeting BCL2 can overcome resistance and enhance sensitivity to AURKB inhibition in SCLC.
CLINICAL CANCER RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Yan Zhong, Lin Deng, Shuo Shi, Qiu-yao Huang, Shu-min Ou-Yang, Jian-shan Mo, Kai Zhu, Xin-ming Qu, Pei-qing Liu, Yuan-xiang Wang, Xiao-lei Zhang
Summary: The small molecule WZ-2-033 has shown promising results in inhibiting STAT3 activation and dimerization, as well as suppressing tumor growth, migration, and invasion in TNBC and gastric cancer cells with aberrant STAT3 activation.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Inken Floerkemeier, Julia S. Hillmann, Joerg P. Weimer, Jonas Hildebrandt, Nina Hedemann, Christoph Rogmans, Astrid Dempfle, Norbert Arnold, Bernd Clement, Dirk O. Bauerschlag
Summary: Although ovarian cancer is rare, it is the fifth leading cause of cancer death among women. This study explores the potential benefits of combining P8-D6, a dual topoisomerase inhibitor, with olaparib, a PARP inhibitor targeting DNA damage repair, in the treatment of ovarian cancer. The combination therapy shows promise in reducing the required dosage while maintaining efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jiali Hu, Ruitao Lu, Yu Zhang, Wei Li, Qian Hu, Cuiyu Chen, Zhaoqian Liu, Wei Zhang, Ling Chen, Ran Xu, Jia Luo, Howard L. McLeod, Yijing He
Summary: The study demonstrates that propranolol pretreatment can enhance the propagation and therapeutic efficacy of T1012G virus in gastric cancer by regulating the STAT3-PKR signaling cascade, even in the presence of type I interferons.
CELL AND BIOSCIENCE
(2021)
Article
Oncology
Kristina Witt, Susan Evans-Axelsson, Andreas Lundqvist, Martin Johansson, Anders Bjartell, Rebecka Hellsten
Summary: The combination of STAT3 inhibition with anti-CTLA-4 therapy enhances antitumoral activity in prostate cancer, reducing intratumoral Treg frequency.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Haobin Li, Maohua Cai, Fei Cao, Dehua Yu, Jing Yang, Wenkai Yu, Chu Chu, Xiaoqing Guan, Jiang-Jiang Qin, Jinyun Dong
Summary: A series of new STAT3 inhibitors were synthesized and the representative compound SIL-14 demonstrated strong anti-proliferation activity, inhibited colony formation and migration of gastric cancer cells, and induced cell apoptosis. It also inhibited the STAT3 signaling pathway, indicating its potential as an anticancer agent.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Tao Wang, Peng Zhang, Chengguo Li, Weizhen Liu, Qian Shen, Lei Yang, Gengchen Xie, Jie Bai, Ruidong Li, Kaixiong Tao, Yuping Yin
Summary: MUS81 is a key regulator of cell cycle distribution and DNA damage repair in gastric cancer. Inhibition of MUS81 enhances the anticancer effect of the PARP inhibitor talazoparib by impairing the activation of the ATR/CHK1 cell cycle signaling pathway and promoting continued mitosis in gastric cancer cells with talazoparib-induced DNA damage. Additionally, the combination of the bromodomain-containing protein 4 inhibitor AZD5153 with talazoparib further enhances the anticancer effect, which is largely impaired when MUS81 is knocked down.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Peng He, Aiwu Bian, Ying Miao, Wangrui Jin, Huang Chen, Jia He, Liting Li, Yue Sun, Jiangnan Ye, Zhengfang Yi, Wenbo Zhou, Yihua Chen
Summary: This study reports the discovery of a series of novel STAT3 dual phosphorylation inhibitors with an indole-containing tetra-aromatic heterocycle scaffold. The optimal compound 4c showed desirable ADME properties and highly potent antitumor activities in vitro and in vivo. It has the potential to be a useful treatment option for pancreatic cancer as a STAT3 dual phosphorylation inhibitor.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Kyle A. Rohrer, Heyu Song, Anum Akbar, Yingling Chen, Suravi Pramanik, Phillip J. Wilder, Erin M. McIntyre, Nagendra K. Chaturvedi, Kishor K. Bhakat, Angie Rizzino, Don W. Coulter, Sutapa Ray
Summary: Medulloblastoma (MB) is a common childhood malignant brain tumor that accounts for a significant percentage of pediatric central nervous system tumors. This study reveals the functional role of activated STAT3 in promoting MB tumorigenesis and chemoresistance by inducing the oncogene MYC. Inhibiting STAT3 can reduce the growth and survival of MB cells and improve treatment efficacy, especially in high-risk MYC-amplified tumors.
Article
Oncology
Guiqin Xie, Ailin Zhu, Xinbin Gu
Summary: Hepatocellular carcinoma (HCC) is a common and deadly liver cancer. Targeting CDK7 with THZ1 may be a promising therapeutic strategy for HCC, especially in cells with high MYC expression levels. The combination of MYC-promoted cell cycle progression and CDK7 inhibition by THZ1 enhances the sensitivity of HCC cells to DNA-damage-induced cell death.