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Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects Mol. Cancer (IF 37.3) Pub Date : 2024-03-16 Yufei Wang, Alicia Buck, Brandon Piel, Luann Zerefa, Nithyassree Murugan, Christian D. Coherd, Andras G. Miklosi, Haraman Johal, Ricardo Nunes Bastos, Kun Huang, Miriam Ficial, Yasmin Nabil Laimon, Sabina Signoretti, Zhou Zhong, Song-My Hoang, Gabriella M. Kastrunes, Marion Grimaud, Atef Fayed, Hsien-Chi Yuan, Quang-De Nguyen, Tran Thai, Elena V. Ivanova, Cloud P. Paweletz, Ming-Ru Wu, Toni K. Choueiri
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated
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The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN Mol. Cancer (IF 37.3) Pub Date : 2024-03-16 Tao Jiang, Junwen Qi, Zhenyu Xue, Bowen Liu, Jianquan Liu, Qihang Hu, Yuqiu Li, Jing Ren, Hu Song, Yixin Xu, Teng Xu, Ruizhi Fan, Jun Song
Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY
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A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation Mol. Cancer (IF 37.3) Pub Date : 2024-03-14 Xin Peng, Xin Huang, Talal Ben Lulu, Wenqing Jia, Shaolu Zhang, Limor Cohen, Shengfan Huang, Jindian Fan, Xi Chen, Shanshan Liu, Yongzhe Wang, Kailin Wang, Sho Isoyama, Shingo Dan, Feng Wang, Zhe Zhang, Moshe Elkabets, Dexin Kong
Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some
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The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments Mol. Cancer (IF 37.3) Pub Date : 2024-03-11 Tao Chen, Jieyi Deng, Yongli Zhang, Bingfeng Liu, Ruxin Liu, Yiqiang Zhu, Mo Zhou, Yingtong Lin, Baijin Xia, Keming Lin, Xiancai Ma, Hui Zhang
Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. Here, we tried
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Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Xiaojun Shi, Shiyu Pang, Jiawei Zhou, Guang Yan, Ruxi Gao, Haowei Wu, Zhou Wang, Yuqing Wei, Xinyu Liu, Wanlong Tan
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3)
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Correction: Aurora kinase targeting in lung cancer reduces KRAS-induced transformation Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Edmilson Ozorio dos Santos, Tatiana Correa Carneiro-Lobo, Mateus Nobrega Aoki, Elena Levantini, Daniela Sanchez Bassères
Correction: Mol Cancer 15, 12 (2016) https://doi.org/10.1186/s12943-016-0494-6 Following publication of the original article [1], the authors identified an error in Fig. 1f. The correct and incorrect figures are given below. Incorrect Fig. 1: Correct Fig. 1: Fig. 1 shRNA-mediated knockdown of AURKA or AURKB decreases the transformed phenotype of KRAS-positive lung cells. Unless otherwise indicated
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Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine Mol. Cancer (IF 37.3) Pub Date : 2024-03-09 Anmi Jose, Pallavi Kulkarni, Jaya Thilakan, Murali Munisamy, Anvita Gupta Malhotra, Jitendra Singh, Ashok Kumar, Vivek M. Rangnekar, Neha Arya, Mahadev Rao
Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved
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Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Cuncan Deng, Mingyu Huo, Hongwu Chu, Xiaomei Zhuang, Guofei Deng, Wenchao Li, Hongfa Wei, Leli Zeng, Yulong He, Huashan Liu, Jia Li, Changhua Zhang, Hengxing Chen
Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is
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Activation of the PI3K/AKT signaling pathway by ARNTL2 enhances cellular glycolysis and sensitizes pancreatic adenocarcinoma to erlotinib Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Weiyu Ge, Yanling Wang, Ming Quan, Tiebo Mao, Evelyne Y. Bischof, Haiyan Xu, Xiaofei Zhang, Shumin Li, Ming Yue, Jingyu Ma, Haiyan Yang, Lei Wang, Zhengyuan Yu, Liwei Wang, Jiujie Cui
Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase
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circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Yan Zhao, Yunlong Jia, Jiali Wang, Xiaolin Chen, Jingya Han, Shuman Zhen, Shuxian Yin, Wei Lv, Fan Yu, Jiaqi Wang, Fan Xu, Xinming Zhao, Lihua Liu
Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain
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Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response Mol. Cancer (IF 37.3) Pub Date : 2024-03-08 Hailong Qi, Zhongjie Sun, Tianle Gao, Yanling Yao, Yu Wang, Weiwei Li, Xudong Wang, Xiaofang Wang, Defang Liu, Jian-Dong Jiang
Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines
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Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma Mol. Cancer (IF 37.3) Pub Date : 2024-02-29 Jeongsoo Kim, Tae-Jin Kim, Sehyun Chae, Hyojeong Ha, Yejin Park, Sunghee Park, Chul Joo Yoon, Seon Ah Lim, Hyemin Lee, Jiyoung Kim, Jungwon Kim, Kyungtaek Im, Kyunghye Lee, Jeongmin Kim, Daham Kim, Eunju Lee, Min Hwa Shin, Serk In Park, Inmoo Rhee, Keehoon Jung, Jeewon Lee, Keun Hwa Lee, Daehee Hwang, Kyung-Mi Lee
In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific
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Correction: Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis Mol. Cancer (IF 37.3) Pub Date : 2024-02-29 Xiao-Yong Huang, Peng-Fei Zhang, Chuan-Yuan Wei, Rui Peng, Jia-Cheng Lu, Chao Gao, Jia-Bing Cai, Xuan Yang, Jia Fan, Ai-Wu Ke, Jian Zhou, Guo-Ming Shi
Correction: Mol Cancer 19, 92 (2020) https://doi.org/10.1186/s12943-020-01213-6 Following publication of the original article [1], the authors would like to correct an error in Fig. 7d (CD4 and CD8 staining in Hep1-6-Snail tumors treated by PBS, PD1 abs and Sitagliptin. The other Figures of the article remain the same, and the interpretation of the results remains unchanged. The correction does not
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Correction: Comprehensive review of CRISPR‑based gene editing: mechanisms, challenges, and applications in cancer therapy Mol. Cancer (IF 37.3) Pub Date : 2024-02-27 Mohammad Chehelgerdi, Matin Chehelgerdi, Milad Khorramian‑Ghahfarokhi, Marjan Shafieizadeh, Esmaeil Mahmoudi, Fatemeh Eskandari, Mohsen Rashidi, Asghar Arshi, Abbas Mokhtari‑Farsani
Correction: Mol Cancer 23, 9 (2024) https://doi.org/10.1186/s12943-023-01925-5 Following publication of the original article [1], it has come to the author's attention that this article cites their work in an incorrect fashion and at least the related part of the paper raises some concern about the integrity of the reported information. In Table 3 on clinical trials of CRISPR-based therapy of the manuscript
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Activation-induced cytidine deaminase causes recurrent splicing mutations in diffuse large B-cell lymphoma Mol. Cancer (IF 37.3) Pub Date : 2024-02-24 Maria S. Benitez-Cantos, Carlos Cano, Marta Cuadros, Pedro P. Medina
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma. A major mutagenic process in DLBCL is aberrant somatic hypermutation (aSHM) by activation-induced cytidine deaminase (AID), which occurs preferentially at RCH/TW sequence motifs proximal to transcription start sites. Splice sequences are highly conserved, rich in RCH/TW motifs, and recurrently mutated in DLBCL. Therefore, we hypothesized
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Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer Mol. Cancer (IF 37.3) Pub Date : 2024-02-24 Anna Solta, Büsra Ernhofer, Kristiina Boettiger, Zsolt Megyesfalvi, Simon Heeke, Mir Alireza Hoda, Christian Lang, Clemens Aigner, Fred R. Hirsch, Karin Schelch, Balazs Döme
Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on
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The therapeutically actionable long non-coding RNA ‘T-RECS’ is essential to cancer cells’ survival in NRAS/MAPK-driven melanoma Mol. Cancer (IF 37.3) Pub Date : 2024-02-22 Valentin Feichtenschlager, Linan Chen, Yixuan James Zheng, Wilson Ho, Martina Sanlorenzo, Igor Vujic, Eleanor Fewings, Albert Lee, Christopher Chen, Ciara Callanan, Kevin Lin, Tiange Qu, Dasha Hohlova, Marin Vujic, Yeonjoo Hwang, Kevin Lai, Stephanie Chen, Thuan Nguyen, Denise P Muñoz, Yoshinori Kohwi, Christian Posch, Adil Daud, Klemens Rappersberger, Terumi Kohwi-Shigematsu, Jean-Philippe Coppé,
Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in
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Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome Mol. Cancer (IF 37.3) Pub Date : 2024-02-21 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
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). The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin
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Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide Mol. Cancer (IF 37.3) Pub Date : 2024-02-20 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
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Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study Mol. Cancer (IF 37.3) Pub Date : 2024-02-19 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
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Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application Mol. Cancer (IF 37.3) Pub Date : 2024-02-17 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
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CircPCNXL2 promotes tumor growth and metastasis by interacting with STRAP to regulate ERK signaling in intrahepatic cholangiocarcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-02-17 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
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. 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
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A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway Mol. Cancer (IF 37.3) Pub Date : 2024-02-15 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
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. The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were
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ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner Mol. Cancer (IF 37.3) Pub Date : 2024-02-14 Chuanpeng Zhang, Ziyi Yu, Susu Yang, Yitao Liu, Jiangni Song, Juan Mao, Minghui Li, Yi Zhao
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. In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then
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Multicancer screening test based on the detection of circulating non haematological proliferating atypical cells Mol. Cancer (IF 37.3) Pub Date : 2024-02-13 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
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
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Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis Mol. Cancer (IF 37.3) Pub Date : 2024-02-12 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
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Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer Mol. Cancer (IF 37.3) Pub Date : 2024-02-10 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,
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Correction: ERK mediates interferon gamma-induced melanoma cell death Mol. Cancer (IF 37.3) Pub Date : 2024-02-05 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
Correction: Mol Cancer 22, 165 (2023) https://doi.org/10.1186/s12943-023-01868-x Following publication of the original article [1], the authors reported that an author’s last name that appeared in the published online version is incorrect. Robert Damioseaux should be Robert Damoiseaux. Champhekar A, Heymans R, Saco J, et al. ERK mediates interferon gamma-induced melanoma cell death. Mol Cancer. 2023;22:165
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Discrimination of pancreato-biliary cancer and pancreatitis patients by non-invasive liquid biopsy Mol. Cancer (IF 37.3) Pub Date : 2024-02-02 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
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. Differentially methylated regions (DMRs) from plasma cfDNA between PBCs, pancreatitis
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Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4–HDAC4–RUNX2–GAMT-mediated apoptosis Mol. Cancer (IF 37.3) Pub Date : 2024-01-31 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
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)
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Mapping cancer biology in space: applications and perspectives on spatial omics for oncology Mol. Cancer (IF 37.3) Pub Date : 2024-01-30 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
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JAK/STAT in leukemia: a clinical update Mol. Cancer (IF 37.3) Pub Date : 2024-01-26 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
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Pangaea Oncology, Dexeus University Hospital: bridging preclinical and clinical research Mol. Cancer (IF 37.3) Pub Date : 2024-01-25 María González-Cao, Carlos Pedraz, Miguel Ángel Molina-Vila, Rafael Rosell
Pangaea Oncology has a comprehensive clinical trial portfolio: including investigator initiated trials (IITs) which emphasize Pangaea’s novel scientific development, cooperative academic studies, and industry sponsored trials. Clinical trials are the mainstay for bringing out the most promising treatment strategies and drugs to our patients, including patients that do not have private insurance or
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LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM Mol. Cancer (IF 37.3) Pub Date : 2024-01-24 Zehua Bian, Fan Yang, Peiwen Xu, Ge Gao, Chunyu Yang, Yulin Cao, Surui Yao, Xue Wang, Yuan Yin, Bojian Fei, Zhaohui Huang
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. In this study, we investigated the
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Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives Mol. Cancer (IF 37.3) Pub Date : 2024-01-24 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
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The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway Mol. Cancer (IF 37.3) Pub Date : 2024-01-23 Konstantinos Karakostis, Laurence Malbert-Colas, Aikaterini Thermou, Borek Vojtesek, Robin Fåhraeus
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
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Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes Mol. Cancer (IF 37.3) Pub Date : 2024-01-22 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
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Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target Mol. Cancer (IF 37.3) Pub Date : 2024-01-20 Xiaoliang Huang, Weiming Zhang, Na Yang, Yujie Zhang, Tianyu Qin, Hanyi Ruan, Yan Zhang, Chao Tian, Xianwei Mo, Weizhong Tang, Jungang Liu, Beibei Zhang
Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1
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Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance Mol. Cancer (IF 37.3) Pub Date : 2024-01-19 Chi Zhang, Chaoying Qin, Saikat Dewanjee, Hiranmoy Bhattacharya, Pratik Chakraborty, Niraj Kumar Jha, Moumita Gangopadhyay, Saurabh Kumar Jha, Qing Liu
The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation of cancer, through genetic and biological communication with healthy cells. TDSEVs are known to orchestrate the invasion-metastasis cascade via diverse pathways. Regulation of early metastasis processes, pre-metastatic niche formation, immune system regulation
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Patient-specific signaling signatures predict optimal therapeutic combinations for triple negative breast cancer Mol. Cancer (IF 37.3) Pub Date : 2024-01-16 Heba Alkhatib, Jason Conage-Pough, Sangita Roy Chowdhury, Denen Shian, Deema Zaid, Ariel M. Rubinstein, Amir Sonnenblick, Tamar Peretz-Yablonsky, Avital Granit, Einat Carmon, Ishwar N. Kohale, Judy C. Boughey, Matthew P. Goetz, Liewei Wang, Forest M. White, Nataly Kravchenko-Balasha
Triple negative breast cancer (TNBC) is a heterogeneous group of tumors which lack estrogen receptor, progesterone receptor, and HER2 expression. Targeted therapies have limited success in treating TNBC, thus a strategy enabling effective targeted combinations is an unmet need. To tackle these challenges and discover individualized targeted combination therapies for TNBC, we integrated phosphoproteomic
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Correction: hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-01-16 Lei Xu, Xiao Ma, Xiuzhong Zhang, Chong Zhang, Yi Zhang, Shuai Gong, Nai Wu, Peng Zhang, Xinyu Feng, Jiaxuan Guo, Mengmeng Zhao, Zeqiang Ren, Pengbo Zhang
Correction: Mol Cancer 22, 195 (2023) https://doi.org/10.1186/s12943-023-01887-8 Following publication of the original article [1], the authors found that the grouping tags in Fig. 1A was mislabeled and led to completely opposite representations, so they would like to correct the picture. The correct figure is given below. Fig. 1 hsa_circ_0007919 is upregulated in GEM-resistant PDAC and predicts poor
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Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments Mol. Cancer (IF 37.3) Pub Date : 2024-01-15 Dong-Xu Wang, Jun-Yu Long, Rui-Zhe Li, Dao-Lin Zhang, Hui Liu, Jingru Liu, Jin-Cheng Tian, Han Li, Jie Liu, Hai-Tao Zhao, Tao Li
Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings
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Correction: Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer Mol. Cancer (IF 37.3) Pub Date : 2024-01-15 Jianan Chen, Yan Yu, Hua Li, Qiuyue Hu, Xiaolong Chen, Yuting He, Chen Xue, Fang Ren, Zhigang Ren, Juan Li, Liwen Liu, Zhenfeng Duan, Guangying Cui, Ranran Sun
Correction: Mol Cancer 18, 33 (2019) https://doi.org/10.1186/s12943-019-0947-9 Following publication of the original article [1], the authors, after thorough checking the original data, they have found three unintentional duplication in this paper, the authors requested to update the figures as stated below. We request to replace the misused image in Fig. 2K with the correct image Fig. 2 The effect
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Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage polarity and prognostic indicators Mol. Cancer (IF 37.3) Pub Date : 2024-01-13 Xinming Su, Chenhao Liang, Ruixiu Chen, Shiwei Duan
The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable
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Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma Mol. Cancer (IF 37.3) Pub Date : 2024-01-10 XiaoChang Fang, Lin Shu, TianLiang Chen, XiaoLe Zhao, LiuCui Yang, Tingting Dou, Lijie Yang, Xuanfei Li, Maohui Feng
Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and
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Aberrant R-loop–mediated immune evasion, cellular communication, and metabolic reprogramming affect cancer progression: a single-cell analysis Mol. Cancer (IF 37.3) Pub Date : 2024-01-10 Shichao Zhang, Yang Liu, Yichi Sun, Qin Liu, Yan Gu, Ya Huang, Zhu Zeng, Fuzhou Tang, Yan Ouyang
Dysregulation of R-loop homeostasis is closely related to various human diseases, including cancer. However, the causality of aberrant R-loops in tumor progression remains unclear. In this study, using single-cell RNA-sequencing datasets from lung adenocarcinoma (LUAD), we constructed an R-loop scoring model to characterize the R-loop state according to the identified R-loop regulators related to EGFR
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Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold Mol. Cancer (IF 37.3) Pub Date : 2024-01-10 Tim Schmäche, Juliane Fohgrub, Anna Klimova, Karin Laaber, Stephan Drukewitz, Felix Merboth, Alexander Hennig, Therese Seidlitz, Friederike Herbst, Franziska Baenke, Anne-Marlen Ada, Thomas Groß, Carina Wenzel, Claudia R. Ball, Christian Praetorius, Thomas Schmidt, Barbara Ringelband-Schilling, Ronald Koschny, Albrecht Stenzinger, Ingo Roeder, Dirk Jaeger, Sebastian Zeissig, Thilo Welsch, Daniela Aust
This study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx). Endoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into culture and PDOs expanded. PDOs' response towards the single substances of the FLOT regimen and the combination treatment were correlated
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Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy Mol. Cancer (IF 37.3) Pub Date : 2024-01-09 Mohammad Chehelgerdi, Matin Chehelgerdi, Milad Khorramian-Ghahfarokhi, Marjan Shafieizadeh, Esmaeil Mahmoudi, Fatemeh Eskandari, Mohsen Rashidi, Asghar Arshi, Abbas Mokhtari-Farsani
The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different
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Evolution of cell therapy for renal cell carcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-01-09 Yufei Wang, Eloah Rabello Suarez, Gabriella Kastrunes, Najla Santos Pacheco de Campos, Rabia Abbas, Renata Schmieder Pivetta, Nithyassree Murugan, Ghanbar Mahmoodi Chalbatani, Vincent D’Andrea, Wayne A. Marasco
Treatment for renal cell carcinoma (RCC) has improved dramatically over the last decade, shifting from high-dose cytokine therapy in combination with surgical resection of tumors to targeted therapy, immunotherapy, and combination therapies. However, curative treatment, particularly for advanced-stage disease, remains rare. Cell therapy as a “living drug” has achieved hematological malignancy cures
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Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age Mol. Cancer (IF 37.3) Pub Date : 2024-01-09 Gillian Seaton, Hannah Smith, Andrea Brancale, Andrew D. Westwell, Richard Clarkson
In the early 1990’s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature ‘Bcl’, and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other
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Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with anti-PDL1 therapy effectively inhibits triple-negative breast cancer growth and metastasis Mol. Cancer (IF 37.3) Pub Date : 2024-01-06 Odd L. Gammelgaard, Mikkel G. Terp, Alexei F. Kirkin, Simone Johansen, Sofie Traynor, Henriette Vever, Per Guldberg, Annette R. Kodahl, Morten F. Gjerstorff, Henrik J. Ditzel
Adoptive cell transfer cancer immunotherapy holds promise for treating disseminated disease, yet generating sufficient numbers of lymphocytes with anti-cancer activity against diverse specificities remains a major challenge. We recently developed a novel procedure (ALECSAT) for selecting, expanding and maturating polyclonal lymphocytes from peripheral blood with the capacity to target malignant cells
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N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation Mol. Cancer (IF 37.3) Pub Date : 2024-01-06 Han Li, Run Lin, Yanna Zhang, Yanni Zhu, Shuting Huang, Jing Lan, Nian Lu, Chuanmiao Xie, Shanyang He, Weijing Zhang
Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. Platinum-resistant
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CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis Mol. Cancer (IF 37.3) Pub Date : 2024-01-06 Zaosong Zheng, Xiangbo Zeng, Yuanchao Zhu, Mengxin Leng, Zhiyong Zhang, Qiong Wang, Xiaocen Liu, Siying Zeng, Yongyuan Xiao, Chenxi Hu, Shiyu Pang, Tong Wang, Bihong Xu, Peidan Peng, Fei Li, Wanlong Tan
Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. High-throughput RNA sequencing techniques
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Correction: CMTM6 overexpression confers trastuzumab resistance in HER2‑positive breast cancer Mol. Cancer (IF 37.3) Pub Date : 2024-01-05 Fei Xing, Hongli Gao, Guanglei Chen, Lisha Sun, Jiayi Sun, Xinbo Qiao, Jinqi Xue, Caigang Liu
Correction: BMC Microbiol Mol Cancer 22, 6 (2023) https://doi.org/10.1186/s12943-023-01716-y Following publication of the original article [1], the authors reported that they spotted two mistakes in the published version. The two mistakes are, (1) wrong group labels in Fig. 2DD and (2) the orders of image panels in Figure S2C and D were mistaken, the images of wound healing at 0 time point in Supplementary
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Therapeutic challenges in peripheral T-cell lymphoma Mol. Cancer (IF 37.3) Pub Date : 2024-01-04 Yunpeng Luan, Xiang Li, Yunqi Luan, Junyu Luo, Qinzuo Dong, Shili Ye, Yuejin Li, Yanmei Li, Lu Jia, Jun Yang, Dong-Hua Yang
Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of hematological malignancies. Compared to our knowledge of B-cell tumors, our understanding of T-cell leukemia and lymphoma remains less advanced, and a significant number of patients are diagnosed with advanced stages of the disease. Unfortunately, the development of drug resistance in tumors leads to relapsed or refractory peripheral
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Circulating cell-free DNA methylation patterns as non-invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles Mol. Cancer (IF 37.3) Pub Date : 2024-01-03 Kazuya Yasui, Toshiaki Toshima, Ryo Inada, Yuzo Umeda, Shuya Yano, Hiroaki Tanioka, Akihiro Nyuya, Toshiyoshi Fujiwara, Takeshi Yamada, Yoshio Naomoto, Ajay Goel, Takeshi Nagasaka
This study investigates methylation patterns in circulating cell-free DNA (ccfDNA) for their potential role in colorectal cancer (CRC) detection and the monitoring of treatment response. Through methylation microarrays and quantitative PCR assays, we analyzed 440 samples from The Cancer Genome Atlas (TCGA) and an additional 949 CRC samples. We detected partial or extensive methylation in over 85% of
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Unveiling the hidden AP-1: revealing the crucial role of AP-1 in ccRCC at single-cell resolution Mol. Cancer (IF 37.3) Pub Date : 2023-12-19 Jie Zheng, Fengling Liu, Cheng Su
Clear cell renal cell carcinoma (ccRCC), as the most common histological subtype of kidney cancer, has been reported to originate primarily from proximal tubule (PT) cells in the kidney. However, the current research on its associated molecular mechanisms remains relatively limited. In our study, we analyzed multiple single-cell multi-omics datasets obtained from various research teams, revealing the
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Targeting CRAF kinase in anti-cancer therapy: progress and opportunities Mol. Cancer (IF 37.3) Pub Date : 2023-12-18 Penglei Wang, Kyle Laster, Xuechao Jia, Zigang Dong, Kangdong Liu
The RAS/mitogen-activated protein kinase (MAPK) signaling cascade is commonly dysregulated in human malignancies by processes driven by RAS or RAF oncogenes. Among the members of the RAF kinase family, CRAF plays an important role in the RAS-MAPK signaling pathway, as well as in the progression of cancer. Recent research has provided evidence implicating the role of CRAF in the physiological regulation
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Acidosis-mediated increase in IFN-γ-induced PD-L1 expression on cancer cells as an immune escape mechanism in solid tumors Mol. Cancer (IF 37.3) Pub Date : 2023-12-15 Philipp Knopf, Dimitri Stowbur, Sabrina H. L. Hoffmann, Natalie Hermann, Andreas Maurer, Valentina Bucher, Marilena Poxleitner, Bredi Tako, Dominik Sonanini, Balaji Krishnamachary, Sanhita Sinharay, Birgit Fehrenbacher, Irene Gonzalez-Menendez, Felix Reckmann, David Bomze, Lukas Flatz, Daniela Kramer, Martin Schaller, Stephan Forchhammer, Zaver M. Bhujwalla, Leticia Quintanilla-Martinez, Klaus Schulze-Osthoff
Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by the heterogeneous and hypoxic tumor microenvironment (TME) of solid tumors. In the TME, programmed death-ligand 1 (PD-L1) expression on cancer cells is mainly regulated by Interferon-gamma (IFN-γ), which induces T cell exhaustion and enables tumor immune evasion. In this study,
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Dynamic altruistic cooperation within breast tumors Mol. Cancer (IF 37.3) Pub Date : 2023-12-14 Muhammad Sufyan Bin Masroni, Kee Wah Lee, Victor Kwan Min Lee, Siok Bian Ng, Chao Teng Law, Kok Siong Poon, Bernett Teck-Kwong Lee, Zhehao Liu, Yuen Peng Tan, Wee Ling Chng, Steven Tucker, Lynette Su-Mien Ngo, George Wai Cheong Yip, Min En Nga, Susan Swee Shan Hue, Thomas Choudary Putti, Boon Huat Bay, Qingsong Lin, Lihan Zhou, Mikael Hartman, Tze Ping Loh, Manikandan Lakshmanan, Sook Yee Lee, Vinay
Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism’s survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells