Article
Multidisciplinary Sciences
Yang Xiao, Fang-Tsyr Lin, Weei-Chin Lin
Summary: ACTL6A overexpression is a novel cause of platinum resistance, associated with chemoresistance in various cancers; Depletion of ACTL6A can increase sensitivity to cisplatin and mediate repair process through the chromatin remodeling complex; Treatment with histone deacetylase inhibitors can reverse the effect of ACTL6A overexpression on cisplatin treatment efficacy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Plant Sciences
Yuzhu Lu, Jia Zeng, Qiaoquan Liu
Summary: This article discusses the function and regulation of rice growth-regulating factors, with a focus on the role of the DELLA protein in GA signaling.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chunming Dong, Rui Zhang, Lijun Xu, Beibei Liu, Xinlei Chu
Summary: This study investigates the assembly mechanism and structure of the multi-subunit ATP-dependent chromatin remodeling factor SWI/SNF complex, as well as the interactions between its subunits. Experimental results demonstrate the assembly mechanism of the core subunit quaternary complexes of the BAF complex and provide crystal structures of corresponding binary complexes. This study provides a theoretical basis for cancer and drug research based on protein structure.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Plant Sciences
Elzbieta Sarnowska, Szymon Kubala, Pawel Cwiek, Sebastian Sacharowski, Paulina Oksinska, Jaroslaw Steciuk, Magdalena Zaborowska, Jakub M. Szurmak, Roman Dubianski, Anna Maassen, Malgorzata Stachowiak, Bruno Huettel, Monika Ciesla, Klaudia Nowicka, Anna T. Rolicka, Saleh Alseekh, Ernest Bucior, Rainer Franzen, Anna Skoneczna, Malgorzata A. Domagalska, Samija Amar, Mohammad-Reza Hajirezaei, Janusz A. Siedlecki, Alisdair R. Fernie, Seth J. Davis, Tomasz J. Sarnowski
Summary: The Arabidopsis ERECTA family of leucine-rich repeat receptor-like kinases (LRR-RLKs) controls various developmental processes and interacts with the SWI/SNF chromatin remodeling complex. The er/erl1/erl2 mutant shows impaired gibberellin signaling, decreased SWI3B protein level, and altered chromatin structure. ERf-SWI/SNF CRC interaction plays an important role in transcriptional control of gibberellin receptors.
Article
Biochemistry & Molecular Biology
Satoshi Takahashi, Rintaro Noro, Masahiro Seike, Chao Zeng, Masaru Matsumoto, Akiko Yoshikawa, Shinji Nakamichi, Teppei Sugano, Mariko Hirao, Kuniko Matsuda, Michiaki Hamada, Akihiko Gemma
Summary: This study identified that CRNDE is associated with the development of resistance to EGFR-TKIs in lung cancer cells. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, restoring sensitivity to EGFR-TKIs. These findings suggest that CRNDE may be a potential therapeutic target for overcoming EGFR-mutant NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Cell Biology
Krystal A. Orlando, Paul A. Wade
Summary: FGFR-altered triple negative breast cancer develops adaptive resistance to FGFR inhibitor therapy, but a new study shows that dual inhibition of YAP or mTORC1 and FGFR has a synergistic effect on tumor growth. This indicates a potential new approach for treating this type of cancer.
NATURE CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yijiang Shi, Daniel Sanghoon Shin
Summary: Lung cancer is a major cause of death worldwide. Molecularly targeted therapeutics and immunotherapy have greatly improved the care of NSCLC patients. However, not all patients benefit from these treatments and reliable biomarkers for immunotherapy are lacking. Alterations of the SWI/SNF chromatin remodeler are common in NSCLC patients, leading to poor response to standard therapies. Different subunits of the SWI/SNF complex have unique impacts on tumorigenesis and treatment response. Further studies are needed to evaluate the impact of SWI/SNF alterations on immunotherapy response in NSCLC patients. Combining inhibitors of chromatin modulators with immunotherapy has shown effectiveness in treating NSCLC with SWI/SNF deficiencies.
Article
Oncology
Molly E. Heft Neal, Andrew C. Birkeland, Apurva D. Bhangale, Jingyi Zhai, Aditi Kulkarni, Susan K. Foltin, Brittany M. Jewell, Megan L. Ludwig, Lisa Pinatti, Hui Jiang, Jonathan B. McHugh, Lawence Marentette, Erin L. McKean, J. Chad Brenner
Summary: This study evaluated the survival outcomes of 46 SNUC patients and identified tobacco use as the only significant predictor of survival. Additionally, it confirmed previously published findings on IDH and SMARC family mutations and discovered novel recurrent aberrations in the JAK/STAT and PI3K pathways. The study also validated a novel PGAP3-SRPK1 gene fusion and showed its negative association with EGFR, E2F, and MYC signaling.
Article
Chemistry, Multidisciplinary
Hai T. Dao, Hengyuan Liu, Nazar Mashtalir, Cigall Kadoch, Tom W. Muir
Summary: This study reports a strategy for controlling the orientation of asymmetric nucleosomes and hexasomes, providing an efficient method for studying gene regulation. By using truncated DNA templates and DNA ligation, the researchers successfully prepared desymmetrized mononucleosomes and oligonucleosomes with varied DNA sequences and histone compositions. Using this technology, they investigated the impact of asymmetry on chromatin remodeling and found that cancer-associated histone mutations can cause aberrant chromatin structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Cell Biology
Mingxuan Li, Yutao Shen, Yujia Xiong, Shuai Wang, Chuzhong Li, Jiwei Bai, Yazhuo Zhang
Summary: The study revealed that SMARCB1 functions as a tumor suppressor in chordoma by inhibiting the malignant phenotype of chordoma cells. SMARCB1 inhibits autophagy through direct binding to the ATG5 promoter, leading to decreased ATG5 expression and impaired autophagy. High ATG5 expression is associated with adverse outcomes in recurrent chordoma patients.
CELL PROLIFERATION
(2021)
Article
Gastroenterology & Hepatology
Feng-Kun Zhang, Qian-Zhi Ni, Kang Wang, Hui-Jun Cao, Dong-Xian Guan, Er-Bin Zhang, Ning Ma, Yi-Kang Wang, Qian-Wen Zheng, Sheng Xu, Bing Zhu, Tian-Wei Chen, Ji Xia, Xiao-Song Qiu, Xu-Fen Ding, Hao Jiang, Lin Qiu, Xiang Wang, Wei Chen, Shu-Qun Cheng, Dong Xie, Jing-Jing Li
Summary: The loss of ARID1A in hepatocellular carcinoma (HCC) cells provides protection against cell death induced by glucose deprivation. ARID1A regulates the USP9X-AMPK axis, and synthetic lethal therapy targeting USP9X may benefit HCC patients with ARID1A mutation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Mateus Mota, Stefan R. Sweha, Matt Pun, Siva Kumar Natarajan, Yujie Ding, Chan Chung, Debra Hawes, Fusheng Yang, Alexander R. Judkins, Susanta Samajdar, Xuhong Cao, Lanbo Xiao, Abhijit Parolia, Arul M. Chinnaiyan, Sriram Venneti
Summary: H3K27M mutations reprogram the SWI/SNF complex, leading to increased levels of SMARCA4, SMARCA2, and PBRM1 proteins. The PROTAC AU-15330 can degrade these proteins and exhibits cytotoxicity in H3K27M cells. Additionally, AU-15330 reduces gene expression, chromatin accessibility, and global H3K27ac levels, resulting in decreased levels of FOXO1 and cell death in H3K27M cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Marie-Isabelle Glueckstein, Sebastian Dintner, Tim Tobias Arndt, Dmytro Vlasenko, Gerhard Schenkirsch, Abbas Agaimy, Gernot Mueller, Bruno Maerkl, Bianca Grosser
Summary: This study investigated the clinical relevance of immunohistochemical expression of SWI/SNF complex proteins in 477 adenocarcinomas of the stomach and gastroesophageal junction. It found that aberrant expression of the complex was present in 32% of cases and was associated with negative prognosis. Determination of SWI/SNF status in genomically stable tumors could help identify patients who might benefit from new therapeutic options.
Review
Biochemistry & Molecular Biology
Alvaro Andrades, Paola Peinado, Juan Carlos Alvarez-Perez, Juan Sanjuan-Hidalgo, Daniel J. J. Garcia, Alberto M. M. Arenas, Ana M. M. Matia-Gonzalez, Pedro P. P. Medina
Summary: Hematological malignancies are diverse diseases with varied molecular characteristics. SWI/SNF chromatin remodeling complexes are important for gene regulation in hematopoietic stem cells. Alterations in SWI/SNF complex subunits, particularly ARID1A/1B/2, SMARCA2/4, and BCL7A, are recurrent in lymphoid and myeloid malignancies. These alterations have clinical potential, as mutations in SWI/SNF subunits can confer resistance to antineoplastic agents and create synthetic lethality relationships with other proteins. SWI/SNF complexes and their subunits may be pharmacologically targeted for the treatment of hematological cancers.
Review
Oncology
Jaren Mullen, Shumei Kato, Jason K. Sicklick, Razelle Kurzrock
Summary: Mutations in ARID1A, a subunit gene of the SWI/SNF chromatin remodeling complex, are common in various cancers and play a crucial role in regulating gene expression related to oncogenesis and tumor suppression. Targeting ARID1A-altered cancers may involve a combination of immune checkpoint blockade and inhibitors of various pathways.ARID1A alterations may also mediate resistance to specific chemotherapies and hormone therapies.
CANCER TREATMENT REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Jing-Hui Li, Reza Forghani, Lionel Bure, Gregory R. Wojtkiewicz, Yue Wu, Yoshiko Iwamoto, Muhammad Ali, Anning Li, Cuihua Wang, Negin Jalali Motlagh, Andreas Papadakis, Marc P. Pusztaszeri, Alan Spatz, Hugh Curtin, Ying-Sheng Cheng, John W. Chen
Summary: In this study, the researchers evaluated the use of molecular immuno-imaging targeting myeloperoxidase (MPO) activity for the detection and delineation of head and neck squamous cell carcinoma (HNSCC). They found that MPO imaging was superior to conventional imaging agents in detecting tumor extent, and it correlated strongly with tumor size on histology. Furthermore, MPO imaging detected early tumors that were not visualized with the conventional agent. The results suggest that MPO imaging could improve tumor resection and serve as a useful imaging biomarker for tumor progression in HNSCC.
Article
Biochemistry & Molecular Biology
Yan Li, Chen Yang, Zhicheng Liu, Shangce Du, Susan Can, Hailin Zhang, Linmeng Zhang, Xiaowen Huang, Zhenyu Xiao, Xiaobo Li, Jingyuan Fang, Wenxin Qin, Chong Sun, Cun Wang, Jun Chen, Huimin Chen
Summary: Functional genetic immuno-oncology screens have been used to identify potential regulators in tumor-immune interactions. This study collected and analyzed the data from these screens and identified 105 regulator genes. A novel immune-oncology target called MON2 was also discovered. Furthermore, a signature named CTIS was developed to predict response to immune checkpoint blockade and improve the efficacy of immunotherapy agents.
Article
Multidisciplinary Sciences
Barbara Steurer, Roel C. Janssens, Marit E. Geijer, Fernando Aprile-Garcia, Bart Geverts, Arjan F. Theil, Barbara Hummel, Martin E. van Royen, Bastiaan Evers, Rene Bernards, Adriaan B. Houtsmuller, Ritwick Sawarkar, Jurgen Marteijn
Summary: DNA damage inhibits RNA polymerase II from elongating, but also triggers genome-wide transcriptional responses. Particularly, promoter-bound Pol II is degraded in a GSK3 signaling-mediated response, which is crucial for cells to cope with DNA damage-induced transcription stress.
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Tracy L. Stockley, Bryan Lo, Adrian Box, Andrea Gomez Corredor, John DeCoteau, Patrice Desmeules, Harriet Feilotter, Daria Grafodatskaya, Wenda Greer, Cynthia Hawkins, Weei Yuarn Huang, Iyare Izevbaye, Guylaine Lepine, Sebastiao N. Martins Filho, Andreas I. Papadakis, Paul C. Park, Jean-Baptiste Riviere, Brandon S. Sheffield, Alan Spatz, Elizabeth Spriggs, Tran-Thanh Danh, Stephen Yip, Tong Zhang, Emina Torlakovic, Ming Sound Tsao
Summary: The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring study conducted to optimize testing for neurotrophic receptor tyrosine kinase (NTRK) fusions in Canadian laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) for NTRK1, NTRK2, or NTRK3 fusions, and panels like Oncomine Comprehensive Assay v3, Oncomine Focus Assay, and FusionPlex Lung showed competence in detecting all fusions.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Review
Biotechnology & Applied Microbiology
Haojie Jin, Liqin Wang, Rene Bernards
Summary: In the past two decades, advancements in understanding the genetic defects underlying cancer have led to the development of numerous targeted cancer drugs. However, resistance to single-agent therapies remains a major hurdle. Rational drug combinations based on a deep understanding of the molecular mechanisms associated with therapy resistance hold great potential in cancer treatment. This article discusses the mechanisms of resistance to targeted therapies and the identification of effective drug combinations to overcome resistance, as well as the challenges in clinically developing these combinations and future perspectives.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Review
Gastroenterology & Hepatology
Chen Yang, Hailin Zhang, Linmeng Zhang, Andrew X. Zhu, Rene Bernards, Wenxin Qin, Cun Wang
Summary: This review summarizes the latest clinical advances in the treatment of advanced hepatocellular carcinoma, including molecular-targeted monotherapies, immuno-oncology monotherapies, combination therapies and novel therapeutic approaches.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Xin Lei, Indu Khatri, Tom de Wit, Iris de Rink, Marja Nieuwland, Ron Kerkhoven, Hans van Eenennaam, Chong Sun, Abhishek D. Garg, Jannie Borst, Yanling Xiao
Summary: Despite their low abundance, cDC1s play a crucial role in anti-cancer immunity and are positively associated with patient survival. This study demonstrates that contact with activated CD4(+) T-cells enables cDC1s to induce a CTL response. The transcriptomic signature of helped cDC1s correlates with tumor infiltration by CTLs, Thelper(h)-1 cells, and overall survival.
NATURE COMMUNICATIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Christian Steinberg, Nathalie Gaudreault, Andreas Papadakis, Cyndi Henry, Jean Champagne, Francois Philippon, Gilles O'Hara, Louis Blier, Benoit Plourde, Isabelle Nault, Karine Roy, Jean-Francois Sarrazin, Alan Spatz, Yohan Bosse
Summary: This study assessed the role of micro-RNAs from peripheral blood as candidate biomarkers in Brugada syndrome. It found that Brugada patients have a distinct micro-RNA expression profile compared with unaffected control individuals, and miR-145-5p and miR-585-3p are associated with the symptom status of Brugada patients, showing potential as prognostic biomarkers for Brugada syndrome.
Article
Oncology
Rene Bernards
Summary: The emergence of new targeted cancer drugs necessitates a complete overhaul in the design of early clinical trials. Rene Bernards explores the need for novel clinical trial designs and the ongoing efforts to achieve this. These innovative trials have the potential to provide similar outcomes for cancer patients with reduced side effects and a decreased cost of cancer care.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Kevin M. Ryan, Jane Smith, Rene Bernards
Summary: The formation of organizations and societies in scientific research facilitates communication, collaboration, and career development. Partnerships between organizations can further enhance these benefits. This article highlights a new partnership between the European Association for Cancer Research (EACR) and Molecular Oncology, a journal owned by the Federation of European Biochemical Societies (FEBS).
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Roy Moscona, Sanne Marlijn Janssen, Mounib Elchebly, Andreas Ioannis Papadakis, Eitan Rubin, Alan Spatz
Summary: BORIS is a transcription factor that is ectopically expressed in melanoma and contributes to the transition of melanoma cells from an intermediate melanocytic state to a more mesenchymal-like state, leading to increased invasion and tumor progression.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Article
Oncology
Beiping Miao, Zhaoqing Hu, Riccardo Mezzadra, Lotte Hoeijmakers, Astrid Fauster, Shangce Du, Zhi Yang, Melanie Sator-Schmitt, Helena Engel, Xueshen Li, Caroline Broderick, Guangzhi Jin, Raquel Gomez-Eerland, Lisette Rozeman, Xin Lei, Hitoshi Matsuo, Chen Yang, Ingrid Hofland, Dennis Peters, Annegien Broeks, Elke Laport, Annika Fitz, Xiyue Zhao, Mohamed A. A. Mahmoud, Xiujian Ma, Sandrine Sander, Hai-kun Liu, Guoliang Cui, Yu Gan, Wei Wu, Yanling Xiao, Albert J. R. Heck, Wenxian Guan, Scott W. Lowe, Hugo M. Horlings, Cun Wang, Thijn R. Brummelkamp, Christian U. Blank, Ton N. M. Schumacher, Chong Sun
Summary: The dysregulation of immune checkpoint molecules allows cancer cells to escape immune destruction. CD58, an important costimulatory ligand, is found to be positively regulated by CMTM6, which also interacts with PD-L1. The presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and the response to PD-L1-PD-1 blockade.
Article
Oncology
Saba Alsaddah, Andreas I. Papadakis, Nora Wong, Laura Palma, David Szlachtycz, Tania Cruz Marino, Pierre-Olivier Fiset, William Foulkes
Summary: This article reports a case of familial lung adenocarcinoma caused by a rare germline missense variant in exon 21 of EGFR. The variant coexisted with another known pathogenic EGFR variant in the tumor. The article highlights the complexity of lung cancer predisposition factor evaluation and proposes an algorithm for identifying at-risk individuals and families.
Article
Oncology
Jason S. Agulnik, Andreas I. Papadakis, Carmela Pepe, Lama Sakr, David Small, Hangjun Wang, Goulnar Kasymjanova, Alan Spatz, Victor Cohen
Summary: This study demonstrates the utility of plasma ctDNA as a noninvasive biomarker for detecting resistance mutations, monitoring treatment response and tumor progression in lung cancer patients. The detection of original mutations at baseline predicts poor progression-free survival and overall survival. The clearance and re-emergence of driver mutations during TKI treatment effectively identifies disease progression.
Review
Oncology
Liqin Wang, Lina Lankhorst, Rene Bernards
Summary: This review discusses how senescence can be induced in cancer cells and how the distinctive features of senescent cancer cells can be exploited for selective eradication. It also explores activation of the host immune system as an attractive way to clear senescent cancer cells, and the potential benefits of a sequential treatment approach with pro-senescence therapy followed by senolytic therapy.
NATURE REVIEWS CANCER
(2022)
