Felix Broghammer, Irina Korovina, Mahesh Gouda, Martina Celotti, Johan van Es, Inga Lange, Cornelia Brunner, Jovan Mircetic, Robert P Coppes, Olivier Gires, Andreas Dahl, Michael Seifert, Nils Cordes
BACKGROUND: Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC). METHODS: The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation...
February 21, 2024: Molecular Cancer
Maud Toulmonde, Jean-Philippe Guegan, Mariella Spalato-Ceruso, Florent Peyraud, Michèle Kind, Lucile Vanhersecke, François Le Loarer, Raul Perret, Coralie Cantarel, Carine Bellera, Alban Bessede, Antoine Italiano
Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures...
February 20, 2024: Molecular Cancer
Cheng-Ming Sun, Maud Toulmonde, Mariella Spalato-Ceruso, Florent Peyraud, Alban Bessede, Michèle Kind, Sophie Cousin, Xavier Buy, Jean Palussiere, Antoine Bougouin, Catherine Sautès-Fridman, Hervé Wolf Fridman, Marina Pulido, Antoine Italiano
Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas...
February 19, 2024: Molecular Cancer
Shuochen Liu, Yirui Wang, Tianlin Wang, Kuangheng Shi, Shilong Fan, Chang Li, Ruixiang Chen, Jifei Wang, Wangjie Jiang, Yaodong Zhang, Yananlan Chen, Xiao Xu, Yue Yu, Changxian Li, Xiangcheng Li
BACKGROUND: circular RNAs (circRNAs) have been reported to exert important effects in the progression of numerous cancers. However, the functions of circRNAs in intrahepatic cholangiocarcinoma (ICC) are still unclear. METHODS: circPCNXL2 (has_circ_0016956) were identified in paired ICC by circRNA microarray. Then, we assessed the biological functions of circPCNXL2 by CCK8, EdU, clone formation, transwell, wound healing assays, and xenograft models. RNA pull-down, mass spectrometry, and RNA immunoprecipitation (RIP) were applied to explore the interaction between cirrcPCNXL2 and serine-threonine kinase receptor-associated protein (STRAP)...
February 17, 2024: Molecular Cancer
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance...
February 17, 2024: Molecular Cancer
Bo Huang, Junwu Ren, Qiang Ma, Feifei Yang, Xiaojuan Pan, Yuying Zhang, Yuying Liu, Cong Wang, Dawei Zhang, Ling Wei, Lingyu Ran, Hongwen Zhao, Ce Liang, Xiaolin Wang, Shiming Wang, Haiping Li, Hao Ning, Ai Ran, Wei Li, Yongquan Wang, Bin Xiao
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. METHODS: The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database...
February 15, 2024: Molecular Cancer
Chuanpeng Zhang, Ziyi Yu, Susu Yang, Yitao Liu, Jiangni Song, Juan Mao, Minghui Li, Yi Zhao
BACKGROUND: Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. METHODS: In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR...
February 14, 2024: Molecular Cancer
Natalia Malara, Maria Laura Coluccio, Fabiana Grillo, Teresa Ferrazzo, Nastassia C Garo, Giuseppe Donato, Annamaria Lavecchia, Franco Fulciniti, Anna Sapino, Eliano Cascardi, Antonella Pellegrini, Prassede Foxi, Cesare Furlanello, Giovanni Negri, Guido Fadda, Arrigo Capitanio, Salvatore Pullano, Virginia M Garo, Francesca Ferrazzo, Alarice Lowe, Angela Torsello, Patrizio Candeloro, Francesco Gentile
BACKGROUND: the problem in early diagnosis of sporadic cancer is understanding the individual's risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation...
February 13, 2024: Molecular Cancer
Peng Wu, Chaoqi Zhang, Xiaoya Tang, Dongyu Li, Guochao Zhang, Xiaohui Zi, Jingjing Liu, Enzhi Yin, Jiapeng Zhao, Pan Wang, Le Wang, Ruirui Li, Yue Wu, Nan Sun, Jie He
Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method...
February 12, 2024: Molecular Cancer
Tianlei Xie, Shan Peng, Shujun Liu, Minghao Zheng, Wenli Diao, Meng Ding, Yao Fu, Hongqian Guo, Wei Zhao, Junlong Zhuang
Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions...
February 10, 2024: Molecular Cancer
Ameya Champhekar, Rachel Heymans, Justin Saco, Guillem Turon Font, Cynthia Gonzalez, Anne Gao, John Pham, June Lee, Ryan Maryoung, Egmidio Medina, Katie M Campbell, Daniel Karin, David Austin, Robert Damioseaux, Antoni Ribas
No abstract text is available yet for this article.
February 5, 2024: Molecular Cancer
Christina Hartwig, Jan Müller, Hagen Klett, Dina Kouhestani, Anke Mittelstädt, Anna Anthuber, Paul David, Maximilian Brunner, Anne Jacobsen, Karolina Glanz, Izabela Swierzy, Lotta Roßdeutsch, Bettina Klösch, Robert Grützmann, Timo Wittenberger, Kai Sohn, Georg F Weber
BACKGROUND: Current diagnostics for the detection of pancreato-biliary cancers (PBCs) need to be optimized. We therefore propose that methylated cell-free DNA (cfDNA) derived from non-invasive liquid biopsies serves as a novel biomarker with the ability to discriminate pancreato-biliary cancers from non-cancer pancreatitis patients. METHODS: Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis and clinical control samples conditions were identified by next-generation sequencing after enrichment using methyl-binding domains and database searches to generate a discriminatory panel for a hybridization and capture assay with subsequent targeted high throughput sequencing...
February 2, 2024: Molecular Cancer
Hao Yuan, Chuang Chen, Haonan Li, Gexi Qu, Luyao Chen, Yaxing Liu, Yufeng Zhang, Qiang Zhao, Changhong Lian, Aifang Ji, Xuedong Hou, Xinjian Liu, Kuirong Jiang, Yi Zhu, Yuan He
BACKGROUND: Pancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC. METHODS: qRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues...
January 31, 2024: Molecular Cancer
Sumin Lee, Gyeongjun Kim, JinYoung Lee, Amos C Lee, Sunghoon Kwon
Technologies to decipher cellular biology, such as bulk sequencing technologies and single-cell sequencing technologies, have greatly assisted novel findings in tumor biology. Recent findings in tumor biology suggest that tumors construct architectures that influence the underlying cancerous mechanisms. Increasing research has reported novel techniques to map the tissue in a spatial context or targeted sampling-based characterization and has introduced such technologies to solve oncology regarding tumor heterogeneity, tumor microenvironment, and spatially located biomarkers...
January 30, 2024: Molecular Cancer
Dong Liang, Qiaoli Wang, Wenbiao Zhang, Hailin Tang, Cailu Song, Zhimin Yan, Yang Liang, Hua Wang
Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field...
January 26, 2024: Molecular Cancer
María González-Cao, Carlos Pedraz, Miguel Ángel Molina-Vila, Rafael Rosell
No abstract text is available yet for this article.
January 25, 2024: Molecular Cancer
Zehua Bian, Fan Yang, Peiwen Xu, Ge Gao, Chunyu Yang, Yulin Cao, Surui Yao, Xue Wang, Yuan Yin, Bojian Fei, Zhaohui Huang
BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. METHODS: In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance...
January 24, 2024: Molecular Cancer
Jiaxi Liu, Yongya Wu, Sha Meng, Ping Xu, Shutong Li, Yong Li, Xiuying Hu, Liang Ouyang, Guan Wang
Eukaryotic cells engage in autophagy, an internal process of self-degradation through lysosomes. Autophagy can be classified as selective or non-selective depending on the way it chooses to degrade substrates. During the process of selective autophagy, damaged and/or redundant organelles like mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes, and lipid droplets are selectively recycled. Specific cargo is delivered to autophagosomes by specific receptors, isolated and engulfed...
January 24, 2024: Molecular Cancer
Konstantinos Karakostis, Laurence Malbert-Colas, Aikaterini Thermou, Borek Vojtesek, Robin Fåhraeus
BACKGROUND: The ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating the MDM2 protein, which develops an affinity for the p53 mRNA secondary structure. Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein-p53 mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the p53 mRNA in the DNA damage sensing mechanism, are still highly anticipated. METHODS: The proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein-mRNA and protein-protein interactions...
January 23, 2024: Molecular Cancer
Huai Liu, Ling Tang, Yanxian Li, Wenji Xie, Ling Zhang, Hailin Tang, Tengfei Xiao, Hongmin Yang, Wangning Gu, Hui Wang, Pan Chen
The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC...
January 22, 2024: Molecular Cancer
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