Article
Environmental Sciences
Chih-Ming Su, Tung-Wei Hsu, Shian-Ying Sung, Ming-Te Huang, Kuan-Chou Chen, Chih-Yang Huang, Chien Yi Chiang, Yen-Hao Su, Hsin-An Chen, Po-Hsiang Liao
Summary: Research has shown that NFI-C and NFI-X are important regulators that significantly correlate with the survival of breast cancer patients. E1A post-transcriptionally downregulates AXL expression through NFI, which could have significant implications for breast cancer treatment.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Immunology
Chun-Bong Synn, Sung Eun Kim, Hee Kyu Lee, Min-Hwan Kim, Jae Hwan Kim, Ji Min Lee, Ha Ni Jo, Wongeun Lee, Dong Kwon Kim, Youngseon Byeon, Young Seob Kim, Mi Ran Yun, Chae-Won Park, Jiyeon Yun, Sangbin Lim, Seong Gu Heo, San-Duk Yang, Eun Ji Lee, Seul Lee, Hunmi Choi, You Won Lee, Jae Seok Cho, Do Hee Kim, Sungho Park, Jung-Ho Kim, Yewon Choi, Sung Sook Lee, Beung-Chul Ahn, Chang Gon Kim, Sun Min Lim, Min Hee Hong, Hye Ryun Kim, Kyoung-Ho Pyo, Byoung Chul Cho
Summary: This study evaluated the anti-tumor and anti-metastatic activities of the AXL small-molecule inhibitor SKI-G-801 alone and in combination with anti-PD-1 therapy. The results showed that SKI-G-801 robustly inhibited pAXL expression and significantly suppressed tumor metastasis and growth by enhancing anti-tumor immune responses. The combination of SKI-G-801 and anti-PD-1 therapy had superior survival benefits by inducing more profound T-cell responses.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Review
Oncology
Rumeysa Ozyurt, Bulent Ozpolat
Summary: Early cancer recurrence, driven by resistance to therapeutics, is a major obstacle in triple-negative breast cancer (TNBC). AXL overexpression has been identified as a key determinant in developing acquired resistance to treatment. AXL activation drives cancer progression and is linked to poor patient survival. There are currently no FDA-approved AXL inhibitors, but multiple inhibitors are being tested in clinical settings. This review outlines the functions and regulation of AXL, its role in resistance to therapy, and the current strategies targeting AXL, with a focus on TNBC.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Cell Biology
Xianhui Wang, Leila Kokabee, Mostafa Kokabee, Douglas S. Conklin
Summary: BTK is a soluble tyrosine kinase with important roles in B cells and epithelial cancers. Inhibition of BTK has been approved by the FDA for treating multiple malignancies, showing promising therapeutic potential.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Mai Tanaka, Samantha S. Dykes, Dietmar W. Siemann
Summary: The study found that inhibiting Axl in prostate and breast cancer cells can significantly reduce metastatic potential, and inhibiting Axl signaling in osteoclast precursor cells can also reduce the formation of mature osteoclasts. In vivo, Axl knockdown in prostate and breast cancer cells significantly suppressed the formation and progression of bone metastases. Therefore, therapeutic targeting of Axl may impair tumor metastasis to the bones through neoplastic and host cell signaling axes.
CLINICAL & EXPERIMENTAL METASTASIS
(2021)
Article
Cell Biology
Xue-Hua Du, Shao-Bo Ke, Xin-Yi Liang, Jie Gao, Xiao-Xiao Xie, Lin-Zhi Qi, Xue-Yi Liu, Guo-Yuan Xu, Xiao-Dong Zhang, Run-Lei Du, Shang-Ze Li
Summary: Our study demonstrates that USP14 functions as a deubiquitinase that interacts and stabilizes JNK, promoting MAPK/JNK signaling and colorectal carcinogenesis. Increased expression of USP14 is associated with elevated levels of JNK protein and downstream gene expression in colorectal cancer patients. Inhibition of USP14 reduces cancer cell proliferation and tumorigenesis by downregulating the activation of the MAPK/JNK pathway.
CELL DEATH & DISEASE
(2023)
Article
Chemistry, Medicinal
Rui He, Zhiqiang Song, Yu Bai, Sheng He, Jing Huang, Yongxing Wang, Fengtao Zhou, Weixue Huang, Jing Guo, Zhen Wang, Zheng-Chao Tu, Xiaomei Ren, Zhang Zhang, Jian Xu, Ke Ding
Summary: AXL kinase is crucially involved in cancer tumorigenesis, metastasis, and drug resistance, and multiple AXL inhibitors are currently being investigated in clinical trials. Recent research has highlighted the importance of the N-terminal region of AXL in cell invasiveness, suggesting that targeting AXL degradation could be a more effective therapeutic approach compared to kinase inhibitors. In this study, a series of new AXL PROTAC degraders were discovered, with compound 6n emerging as a potent AXL depletor in TNBC cells. It exhibited superior inhibitory effects on AXL signaling activation, cell proliferation, migration, and invasion compared to the corresponding kinase inhibitor. Additionally, compound 6n showed promising therapeutic potential in patient-derived organoids and a mouse model of MDA-MB-231 cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Yingying Shen, Qingyun Zhu, Maoyu Xiao, Liyang Yin, Wenjie Feng, Jianbo Feng, Jun He, Pei Li, Xiguang Chen, Wenjun Ding, Jing Zhong, Zhaolin Zeng, Zhuoye Xie, Jianghua Liu, Xuyu Zu
Summary: This study found that the small-molecule tyrosine kinase inhibitor DCC-2036 can suppress breast cancer stem cells by inhibiting the AXL and KLF5 proteins. Additionally, DCC-2036 has the potential to increase the effectiveness of chemotherapy for TNBC.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Sijia Liu, Maarten van Dinther, Sophie C. Hagenaars, Yuanzhuo Gu, Thomas B. Kuipers, Hailiang Mei, Maria Catalina Gomez-Puerto, Wilma E. Mesker, Peter ten Dijke
Summary: Triple-negative breast cancer (TNBC) is a challenging subtype due to its aggressive nature and low response to current therapies. Understanding TNBC metastasis may lead to better diagnosis and treatment options. In this study, OPTN was found to play a surprising role in inhibiting TNBC metastasis by suppressing the TGF beta signaling pathway. These findings suggest that OPTN may be a potential target for suppressing TNBC metastasis.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Jia Z. Shen, Zhixin Qiu, Qiulian Wu, Guoxin Zhang, Rebecca Harris, Dahui Sun, Juha Rantala, William D. Barshop, Linjie Zhao, Deguan Lv, Kwang-Ai Won, James Wohlschlegel, Olle Sangfelt, Heike Laman, Jeremy N. Rich, Charles Spruck
Summary: A study has identified FBXO7 as a regulator of the mesenchymal and immune evasion phenotypes of cancer cells. FBXO7 binds and stabilizes SIX1 and EYA2, promoting mesenchymal gene expression and suppressing immune-related pathways. Inhibition of EYA2 activity decreases the mesenchymal phenotype and enhances cancer cell immunogenicity, leading to improved response to immunotherapy.
Article
Oncology
Li Liao, Yin -Ling Zhang, Ling Deng, Chao Chen, Xiao-Yan Ma, Lisa Andriani, Shao-Ying Yang, Shu-Yuan Hu, Fang-Lin Zhang, Zhi-Min Shao, Da-Qiang Li
Summary: PPP1R14B is upregulated in TNBC and promotes cancer progression and paclitaxel resistance through maintaining the phosphorylation and stability of STMN1. It is a potential therapeutic target for TNBC.
Article
Pharmacology & Pharmacy
Sha-Sha Cheng, Yuan-Qing Qu, Jia Wu, Guan-Jun Yang, Hao Liu, Wanhe Wang, Qi Huang, Feng Chen, Guodong Li, Chun-Yuen Wong, Vincent Kam Wai Wong, Dik-Lung Ma, Chung-Hang Leung
Summary: CDK9 inhibition is a potential therapeutic strategy for TNBC, and compound 1 demonstrates promising anti-metastatic activity.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Microbiology
Dan Zhang, Yuanhui Zhao, Xiaoxin You, Susu He, Erguang Li
Summary: RSV infection is a common pulmonary infection in infants and the elderly, but no specific therapeutics are available. In this study, Axl kinase inhibitors were found to reduce RSV infection and promote the expression of antiviral genes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Oncology
Kurt W. Evans, Erkan Yuca, Stephen S. Scott, Ming Zhao, Natalia Paez Arango, Christian X. Cruz Pico, Turcin Saridogan, Maryam Shariati, Caleb A. Class, Christopher A. Bristow, Christopher P. Vellano, Xiaofeng Zheng, Ana Maria Gonzalez-Angulo, Xiaoping Su, Coya Tapia, Ken Chen, Argun Akcakanat, Bora Lim, Debu Tripathy, Timothy A. Yap, Maria Emilia Di Francesco, Giulio F. Draetta, Philip Jones, Timothy P. Heffernan, Joseph R. Marszalek, Funda Meric-Bernstam
Summary: Oxidative phosphorylation is a metabolic vulnerability in triple-negative breast cancer, and inhibiting it with IACS-10759 may enhance efficacy of multiple targeted therapies.
Article
Biochemistry & Molecular Biology
Pearly Shuyi Ng, Klement Foo, Sandra Sim, Gang Wang, Chuhui Huang, Li Hong Tan, Anders Poulsen, Boping Liu, Doris Hui Ying Tee, Nur Huda Binte Ahmad, Sifang Wang, Zhiyuan Ke, May Ann Lee, Zekui P. Kwek, Joma Joy, Jothi Anantharajan, Nithya Baburajendran, Vishal Pendharkar, Vithya Manoharan, Susmitha Vuddagiri, Kanda Sangthongpitag, Jeffrey Hill, Thomas H. Keller, Alvin W. Hung
Summary: This study identified a new indazole-based AXL inhibitor through a fragment-based lead discovery approach, providing a suitable starting point for further optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)