Article
Cell Biology
MC. Rowell, X. Deschenes-Simard, S. Lopes-Paciencia, B. Le Calve, L. Mignacca, P. Kalegari, A. Fernandez-Ruiz, J. Guillon, F. Lessard, V. Bourdeau, S. Igelmann, AM. Duman, Y. Stanom, F. Kottakis, V. Deshpande, V. Krizhanovsky, N. Bardeesy, G. Ferbeyre
Summary: This study found that mutations in K-Ras in pancreatic adenocarcinomas (PDAC) can stimulate the ERK pathway and activate high levels of ERK, leading to cell senescence. However, advanced PDAC lesions show lower levels of ERK activation. Restoring ERK hyperactivation in PDAC can induce cell growth arrest and expression of senescence markers. ERK-dependent senescence in PDAC is characterized by a nucleolar stress response, including selective depletion of nucleolar phosphoproteins and the formation of intranucleolar foci containing RNA polymerase I. Combining ribosome biogenesis inhibitors with ERK hyperactivation can enhance the senescence response in PDAC cells.
Review
Pharmacology & Pharmacy
Sushanta Halder, Soumi Basu, Shobhit P. Lall, Apar K. Ganti, Surinder K. Batra, Parthasarathy Seshacharyulu
Summary: This review discusses the importance of epidermal growth factor receptor (EGFR) in multiple cancers and its role in cellular processes. It also highlights the newly identified pathways, resistance mechanisms, and adverse effects of EGFR inhibitors. The latest research on EGFR/panEGFR inhibitors and the potential of combining them with immune checkpoint inhibitors are summarized. Suggestions for developing specific compounds to target mutations and reducing adverse events are provided.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2023)
Article
Chemistry, Medicinal
Duncan C. Miller, Suzannah J. Harnor, Mathew P. Martin, Richard A. Noble, Stephen R. Wedge, Celine Cano
Summary: This Miniperspective summarizes the evidence for using the extracellular signal-regulated kinase 5 (ERK5) signaling pathway as a drug target in cancer chemotherapy. It discusses the structure of ERK5 and the evolution of structurally distinct chemotypes of ERK5 kinase domain inhibitors. The complexities of ERK5 pharmacology, including paradoxical ERK5 activation by small molecule inhibitors, are also explored.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, General & Internal
Jana K. Striefler, Jens M. Stieler, Christopher C. M. Neumann, Dominik Geisel, Pirus Ghadjar, Marianne Sinn, Thomas Malinka, Johann Pratschke, Sebastian Stintzing, Helmut Oettle, Hanno Riess, Uwe Pelzer
Summary: This study aimed to determine the maximum tolerable dose of lapatinib in combination with platinum-containing chemotherapy in refractory pancreatic cancer, and to evaluate its safety and efficacy. The maximum tolerable dose was found to be 1250 mg/day, and the combination of lapatinib with platinum-containing chemotherapy was deemed safe in patients with refractory pancreatic cancer.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Mai Tanaka, Dietmar W. Siemann
Summary: Dysregulated signaling pathways in cancer cells and the tumor microenvironment, including the Axl and Gas6 pathways, have led to the development of therapeutic agents targeting the Gas6/Axl pathway. Promising results have been observed in both preclinical and clinical settings, indicating potential clinical efficacy of targeting Gas6 and Axl.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nora Dieguez-Martinez, Sergio Espinosa-Gil, Guillermo Yoldi, Elisabet Megias-Roda, Idoia Bolinaga-Ayala, Maria Vinas-Casas, Gokhan Gorgisen, Ines Domingo-Orti, Hector Perez-Montoyo, Jose R. Bayascas, Eva Colas, Xavier Dolcet, Jose M. Lizcano
Summary: Endometrial cancer is the most common gynecologic cancer in developed countries, and its overall survival rate is poor. This study suggests that inhibiting the ERK5/NF-kB pathway can suppress cell proliferation and survival in endometrial cancer and enhance the efficacy of chemotherapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Adrian Sanchez-Fdez, Maria Florencia Re-Louhau, Pablo Rodriguez-Nunez, Dolores Ludena, Sofia Matilla-Almazan, Atanasio Pandiella, Azucena Esparis-Ogando
Summary: Lung cancer remains a common and deadly tumor, with studies showing the importance of the MEK5/ERK5 MAPK pathway in its pathogenesis. Targeting this pathway may present a new therapeutic option for lung cancer treatment.
NPJ PRECISION ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ruijuan Du, Chuntian Huang, Kangdong Liu, Xiang Li, Zigang Dong
Summary: AURKA is overexpressed in cancers and regulates substrate functions through phosphorylation, participating in various classic oncogenic pathways.
Review
Medicine, General & Internal
Lin Jiang, Jingbo Zhang, Yan Xu, Heng Xu, Mengzhao Wang
Summary: The phosphosphatidylinositol-3-kinase (PI3K) signaling pathway plays a crucial role in the development of lung cancer. Traditional treatment methods have limited efficacy, but molecular targeted therapy has improved survival and prognosis for patients. There is a growing body of research focusing on NSCLC and the PI3K signaling pathway.
CHINESE MEDICAL JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
David E. Heppner, Michael J. Eck
Summary: Precision oncology focuses on identifying and targeting key proteins and pathways driving tumorigenesis or tumor cell survival. Historical and recent efforts in developing inhibitors targeting these nodes emphasize the role of understanding protein structure and regulation in inhibitor discovery and characterization. Structural biology has also revealed new avenues in precision cancer drug discovery by uncovering mechanisms of allosteric regulation and vulnerabilities to activating oncogenic mutations.
Review
Oncology
Motahareh Mortazavi, Fatemeh Moosavi, Miriam Martini, Elisa Giovannetti, Omidreza Firuzi
Summary: This study highlights the role of PI3K/AKT/mTOR pathway in pancreatic ductal adenocarcinoma, but clinical studies have not been promising. Patient stratification is identified as a crucial factor.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mehrdad Hashemi, Sahar Hasani, Shima Hajimazdarany, Seyed Reza Mirmazloomi, Sara Makvandy, Abbas Zabihi, Yeganeh Goldoost, Nazanin Gholinia, Amirabbas Kakavand, Alireza Tavakolpournegari, Shokooh Salimimoghadam, Noushin Nabavi, Ali Zarrabi, Afshin Taheriazam, Maliheh Entezari, Kiavash Hushmandi
Summary: This article discusses the critical role of non-coding RNAs (ncRNAs) in regulating the Notch signaling pathway in various cancer hallmarks, including proliferation, apoptosis, autophagy, EMT, invasion, metastasis, and resistance to therapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Pharmacology & Pharmacy
Hanwei Ma, Fahong Wu, Yinliang Bai, Tianwei Wang, Shangxian Ma, Liuqing Guo, Guiyuan Liu, Guangxian Leng, Yin Kong, Youcheng Zhang
Summary: In this study, the effects of licoricidin on gastric cancer cells were comprehensively explored. Licoricidin was found to inhibit proliferation, induce apoptosis, arrest the cell cycle, and inhibit migration and invasion abilities of gastric cancer cells. Through proteomics research, isoprenyl carboxyl methyltransferase (ICMT) was identified as the potential target of licoricidin. Western blot and immunohistochemistry assays confirmed the downregulation of ICMT expression by licoricidin in cells and xenograft tumors. Additionally, licoricidin effectively reduced the level of active Ras-GTP and blocked the phosphorylation of Raf and Erk. These findings suggest that licoricidin exerts its anti-gastric cancer effects via the ICMT/Ras pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jing Huang
Summary: p53, one of the most well-studied tumor suppressors, is mutated or deleted in half of all cancers. Despite over forty years of research, designing therapeutics targeting the p53 pathway remains extremely challenging. Current efforts include developing p53-based gene therapy and targeted therapies, as well as exploiting the immunogenicity of p53 protein for cancer immunotherapy.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Biochemistry & Molecular Biology
James J. Kang, Albert Ko, Sang Hoon Kil, Jon Mallen-St. Clair, Daniel Sanghoon Shin, Marilene B. Wang, Eri S. Srivatsan
Summary: Receptor tyrosine kinases (RTKs) are cell surface receptors that bind growth factor ligands and initiate cellular signaling. Among the 20 classes of RTKs, 7 classes are linked to head and neck cancers (HNCs). The epidermal growth factor receptor (EGFR) is the most studied class of RTK, with overexpression observed in 20% of tumors and a variant III expression seen in 15% of aggressive chemoradiotherapy resistant HNCs. Current treatments include EGFR monoclonal antibodies and inhibitors targeting the EGFR, MAPK, and mTOR pathways, with immunotherapy showing effectiveness in a subset of patients with HNC. Combination therapy of immunotherapy and EGFR monoclonal antibodies is being explored to overcome EGFR resistance.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Oncology
Chengli Song, Lina Wang, Xiaoyan Wu, Kai Wang, Dan Xie, Qi Xiao, Songyu Li, Kui Jiang, Lujian Liao, John R. Yates, Jiing-Dwan Lee, Qingkai Yang
Article
Oncology
Qingkai Yang, Xianming Deng, Bingwen Lu, Michael Cameron, Colleen Fearns, Matthew P. Patricelli, John R. Yates, Nathanael S. Gray, Jiing-Dwan Lee
Article
Oncology
Runqiang Chen, Qingkai Yang, Jiing-Dwan Lee
Article
Biochemistry & Molecular Biology
Run-Qiang Chen, Qing-Kai Yang, Yan-Ling Chen, Vasco A. Oliveira, William S. Dalton, Colleen Fearns, Jiing-Dwan Lee
JOURNAL OF BIOLOGICAL CHEMISTRY
(2009)
Article
Biochemistry & Molecular Biology
Xianming Deng, Nicolas Dzamko, Alan Prescott, Paul Davies, Qingsong Liu, Qingkai Yang, Jiing-Dwan Lee, Matthew P. Patricelli, Tyzoon K. Nomanbhoy, Dario R. Alessi, Nathanael S. Gray
NATURE CHEMICAL BIOLOGY
(2011)
Article
Biochemistry & Molecular Biology
Q. Yang, L. Liao, X. Deng, R. Chen, N. S. Gray, J. R. Yates, J. D. Lee
Article
Neurosciences
Jun Wang, Sen-Lin Xu, Jiang-Jie Duan, Liang Yi, Yu-Feng Guo, Yu Shi, Lin Li, Ze-Yu Yang, Xue-Mei Liao, Jiao Cai, Yan-Qi Zhang, Hua-Liang Xiao, Li Yin, Hao Wu, Jing-Na Zhang, Sheng-Qing Lv, Qing-Kai Yang, Xiao-Jun Yang, Tao Jiang, Xia Zhang, Xiu-Wu Bian, Shi-Cang Yu
NATURE NEUROSCIENCE
(2019)
Article
Medicine, Research & Experimental
Bai Cui, Yuanyuan Luo, Pengfei Tian, Fei Peng, Jinxin Lu, Yongliang Yang, Qitong Su, Bing Liu, Jiachuan Yu, Xi Luo, Liu Yin, Wei Cheng, Fan An, Bin He, Dapeng Liang, Sijin Wu, Peng Chu, Luyao Song, Xinyu Liu, Huandong Luo, Jie Xu, Yujia Pan, Yang Wang, Dangsheng Li, Peng Huang, Qingkai Yang, Lingqiang Zhang, Binhua P. Zhou, Suling Liu, Guowang Xu, Eric W-F Lam, Keith W. Kelley, Quentin Liu
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Cell Biology
Songyu Li, Yixiang Zhang, Na Wang, Rong Guo, Qiaoling Liu, Changsheng Lv, Jinguang Wang, Lina Wang, Qing-kai Yang
CELL DEATH & DISEASE
(2020)
Article
Biochemistry & Molecular Biology
Lina Wang, Chengli Song, Na Wang, Songyu Li, Qiaoling Liu, Zhen Sun, Kai Wang, Shi-Cang Yu, Qingkai Yang
NATURE CHEMICAL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Shuyan Liu, Taishu Wang, Yulin Shi, Lu Bai, Shanshan Wang, Dong Guo, Yang Zhang, Yangfan Qi, Chaoqun Chen, Jinrui Zhang, Yingqiu Zhang, Quentin Liu, Qingkai Yang, Yang Wang, Han Liu
Summary: Liquid-liquid phase separation is a generic approach to studying the dynamic regulation of phase-separated assemblies and the roles of protein posttranslational modifications. USP42, a deubiquitylase, has been identified to play a pivotal role in nuclear speckle phase separation, mRNA splicing, and cancer cell growth. Inhibition of USP42 presents a novel anticancer strategy by targeting phase separation.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biology
Qiaoling Liu, Qi Xiao, Zhen Sun, Bo Wang, Lina Wang, Na Wang, Kai Wang, Chengli Song, Qingkai Yang
Summary: Targeting DNA repair pathway is an important therapeutic strategy for human cancers, but the failure of DNA repair inhibitors to benefit patients greatly necessitates the development of new strategies. This study reveals that EXOSC1 may act as an endogenous source of mutation in KIRC, promoting DNA damages and sensitizing cancer cells to DNA repair inhibitors, indicating that targeting EXOSC1 could be a potential therapeutic approach.
Article
Immunology
Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Qingkai Yang
Summary: Self-nonself discrimination is crucial for the immune system to respond to pathogens while maintaining tolerance. This study investigates how DNA sensors differentiate between self and nonself. The authors found that the DNA condenser spermine enhances cGAS activation and binding, specifically promoting condensation of viral DNA. Depletion of viral DNA-associated spermine reduces cGAS activation and impairs antiviral and anticancer immunity.
Article
Multidisciplinary Sciences
Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Caigang Liu, Qingkai Yang
Summary: The activation of cyclic GMP-AMP synthase (cGAS) is influenced by the mechanical flexibility of DNA, which is determined by DNA-sequence, damage, and length. Low dose radiation can induce cGAS-mediated acute immune surveillance (AIS) through repairable DNAs in a short period of time. This study establishes a direct connection between immunosurveillance and DNA mechanical features.
NATURE COMMUNICATIONS
(2022)
