Review
Pharmacology & Pharmacy
Xuejian Wang, Wenyan Jiang, Yanmei Du, Dongqi Zhu, Jian Zhang, Chunyan Fang, Fang Yan, Zhe-Sheng Chen
Summary: This review article summarizes the treatments and combination therapies that induce feedback activation of AKT, ERK, STAT3, EGFR, FGFR, and HER2/3 signaling pathways to enhance anti-tumor effect or overcome drug resistance. The underlying mechanisms of protein molecules involved in the feedback activation are explored. Clinical trials employing combination treatments to suppress feedback activation and improve therapeutic efficacy of cancer treatments are also reviewed.
DRUG RESISTANCE UPDATES
(2022)
Article
Plant Sciences
Yili Shen, Haijian Cai, Shenjie Ma, Wenjing Zhu, Haiyang Zhao, Jifa Li, Hua Ye, Lehe Yang, Chengguang Zhao, Xiaoying Huang, Zhongxiao Xiao
Summary: Telocinobufagin can inhibit proliferation and metastasis, and induce apoptosis in non-small-cell lung cancer cells. Its mechanism of action involves inhibition of STAT3 phosphorylation and downstream targets, as well as interference with IL-6-induced STAT3 nuclear translocation.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Medicinal
Linxiang Cai, Ying Wang, Hanhua Chen, Yehong Tan, Tao Yang, Shuren Zhang, Zijian Guo, Xiaoyong Wang
Summary: The interplay between breast cancer cells and the tumor microenvironment plays a crucial role in cancer treatment. Abnormal activation of the STAT3 pathway results in immunosuppression and drug resistance. Platinum(IV) complexes SPP and DPP were synthesized to inhibit the JAK2-STAT3 pathway in breast cancer cells and regulate the tumor microenvironment. These complexes showed significant anti-proliferative activity against triple-negative breast cancer cells, suppressed the expression of STAT3 and related proteins, and induced apoptosis. Furthermore, DPP promoted immune responses and showed excellent anticancer activity with low toxicity in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Qiyi Feng, Jie Chen, Jinxing Huang, Xiaojie Li, Xinyi Liu, Chunxiu Xiao, Xiuli Zheng, Xuanming Chen, Jue Li, Zhongwei Gu, Kui Luo, Kai Xiao, Weimin Li
Summary: Cancer stem cells (CSCs) play a critical role in tumor initiation and therapeutic resistance. In this study, the researchers investigate the efficacy of BBI608 in eliminating CSCs in non-small cell lung cancer (NSCLC). By encapsulating BBI608 into redox-responsive polymeric nanoparticles, they improve the bioavailability and tumor accumulation of the drug. The BBI608-loaded nanoparticles show comparable cytotoxicity against lung cancer cells and CSCs, and exhibit superior anti-tumor efficacy in both cell line-derived and patient-derived xenograft models of NSCLC.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Cell Biology
Makio Higuchi, Kenichi Ishiyama, Masahiro Maruoka, Ryosuke Kanamori, Akifumi Takaori-Kondo, Naoki Watanabe
Summary: ATP-competitive inhibitors developed as potential anti-cancer agents can paradoxically induce the activation and downstream phosphorylation cascade of c-Src, enhancing cell growth. This paradoxical effect may provide important clues for the future development of effective and safe cancer treatment.
Article
Oncology
Tae Woo Kim, Yujin Kim, Hyeongseop Keum, Wonsik Jung, Minho Kang, Sangyong Jon
Summary: The cell-permeable STAT3 inhibitory peptide APT(STAT3)-9R has antitumor effects and can remodel the tumor microenvironment in vemurafenib-resistant melanoma. APT(STAT3)-9R treatment reduces the population of immunosuppressive immune cells while increasing the infiltration of cytotoxic T lymphocytes in the tumor microenvironment.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Review
Pharmacology & Pharmacy
Dejuan Sun, Yuanyuan Guo, Piyu Tang, Hua Li, Lixia Chen
Summary: ADP-ribosylation factor 6 (Arf6), a small G-protein, plays important roles in cellular events and cancer progression. Understanding its function and mechanism is essential for future cancer therapy. This review summarizes the structure and roles of Arf6 in cancer, and discusses its potential as a target for protein-protein interaction inhibitors.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Pharmacology & Pharmacy
Po-Chang Shih, Kuo-Ching Mei
Summary: Chemoresistance resulting from cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) leads to inconsistent chemotherapeutic efficacy. The presence of CSCs and EMT allows cancer cells to switch between differentiated and stem-like states, known as cellular plasticity. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is increasingly recognized as a major factor in CSCs and EMT, with preclinical studies showing reversal of chemoresistance through STAT3 pathway inhibition. This review focuses on mechanisms involving STAT3 and its target genes in regulating EMT, and also discusses the status of clinical trials using STAT3 pathway inhibitors.
DRUG DISCOVERY TODAY
(2021)
Review
Medicine, Research & Experimental
Changpeng Chai, Pengfei Ji, Hao Xu, Huan Tang, Zhengfeng Wang, Hui Zhang, Wence Zhou
Summary: Cancer organoids generated from 3D in vitro cell cultures have provided valuable insights into drug resistance mechanisms. These organoids accurately predict drug resistance due to their genomic and transcriptomic similarity to parental cancer cells. Methods for establishing therapy-sensitive and therapy-resistant organoids involve either direct culture from patient samples or induction with anti-cancer drugs. Genomic and transcriptomic analyses and gene editing have identified key targets in drug resistance, including FGFR3, KHDRBS3, lncRP11-536 K7.3, and FBN1. Mechanisms contributing to resistance include metabolic adaptation, DNA damage response activation, apoptosis defects, reduced cellular senescence, cellular plasticity, subpopulation interactions, and gene fusions. Cancer stem cells (CSCs) have also been implicated in drug resistance using organoid technology. Targeting key genes and CSCs in cancer organoids can reverse drug resistance. This review summarizes the applications of organoids in cancer drug resistance research, highlighting their prospects and limitations.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Cell & Tissue Engineering
Hamed Rezayatmand, Mahboobeh Razmkhah, Iman Razeghian-Jahromi
Summary: Drug resistance caused by cancer stem cells (CSCs) is the main reason for the failure and relapse of cancer therapy. CSCs possess the ability to self-renew and differentiate into heterogeneous cancer cells, and play a significant role in metastatic dissemination. Although chemotherapy can destroy most tumor cells, CSCs are left mostly intact, leading to resistance to treatment. It is crucial to understand the key features of drug resistance caused by CSCs in order to develop effective treatment strategies, but there are challenges in differentiating CSCs from normal cells.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Oncology
Xingxin Zhu, Guangyuan Song, Shiyu Zhang, Jun Chen, Xiaoyi Hu, Hai Zhu, Xing Jia, Zequn Li, Wenfeng Song, Jian Chen, Cheng Jin, Mengqiao Zhou, Yongchao Zhao, Haiyang Xie, Shusen Zheng, Penghong Song
Summary: ASGR1-NLK axis is a potential therapeutic strategy in liver cancer. ASGR1 can suppress the progression of liver cancer by promoting the binding of NLK to STAT3 and inhibiting STAT3 phosphorylation.
Article
Multidisciplinary Sciences
Zhibo He, Biao Song, Manling Zhu, Jun Liu
Summary: Through comprehensive analysis of multiple databases, this study found that STAT3 plays a key role in promoting oncogenesis in different types of tumors and can be a potential therapeutic target for cancer treatment. Therefore, it is important to investigate the role of STAT3 using pan-cancer analysis.
SCIENTIFIC REPORTS
(2023)
Review
Pharmacology & Pharmacy
Zi'an Wang, Yueqin Wang, Zeyun Li, Wenhua Xue, Shousen Hu, Xiangzhen Kong
Summary: Cancer is the leading cause of human death today and its treatment process is complex. Drug resistance is a significant issue in cancer treatment, and lipid metabolism has been found to be closely related to drug resistance. Combination therapy may reverse the development of drug resistance and enhance sensitivity to therapeutic drugs.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yi Xiao, Dihua Yu
Summary: This article summarizes the current progress in targeting the tumor microenvironment in both drug development and clinical trials, emphasizing the challenges in intervening in the tumor microenvironment and discussing strategies to maximize therapeutic benefits. New technologies and approaches to better understand the tumor microenvironment are explored in this context.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Hao Sheng, Qi Feng, Qiang Quan, Xiugui Sheng, Peng Zhang
Summary: This study found that STAT3 can directly activate the pentose-phosphate pathway, exerting a pro-oncogenic effect on Taxol resistance in ovarian cancer. Inhibiting STAT3 can decrease G6PD expression and enhance Taxol sensitivity in resistant cells. This research provides a potential therapeutic target for improving the prognosis of ovarian cancer patients.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)