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Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Wenxing Qin, Jia Li, Na Gao, Xiuyan Kong, Liting Guo, Yang Chen, Liang Huang, Xiaobing Chen, Feng Qi
The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared
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Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Zefeng Zhou, Yongming Xia, Ruixiu Chen, Panpan Gao, Shiwei Duan
The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs
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DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Po-Lan Su, Karthik Chakravarthy, Naoki Furuya, Jeremy Brownstein, Jianhua Yu, Meixiao Long, David Carbone, Zihai Li, Kai He
DLL3 acts as an inhibitory ligand that downregulates Notch signaling and is upregulated by ASCL1, a transcription factor prevalent in the small-cell lung cancer (SCLC) subtype SCLC-A. Currently, the therapeutic strategies targeting DLL3 are varied, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies. Although rovalpituzumab
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Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-05-10 Pinli Yue, Fenglong Bie, Jiarun Zhu, Lin-Rui Gao, Zhendiao Zhou, Guangyu Bai, Xiaobing Wang, Ziyi Zhao, Ze-Fen Xiao, Yong Li, Aiping Zhou, Wen-Yang Liu, Yuchen Jiao, Shugeng Gao
Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two
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Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy Mol. Cancer (IF 37.3) Pub Date : 2024-05-09 José L. Blaya-Cánovas, Carmen Griñán-Lisón, Isabel Blancas, Juan A. Marchal, César Ramírez-Tortosa, Araceli López-Tejada, Karim Benabdellah, Marina Cortijo-Gutiérrez, M. Victoria Cano-Cortés, Pablo Graván, Saúl A. Navarro-Marchal, Jaime Gómez-Morales, Violeta Delgado-Almenta, Jesús Calahorra, María Agudo-Lera, Amaia Sagarzazu, Carlos J. Rodríguez-González, Tania Gallart-Aragón, Christina Eich, Rosario
Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery and efficacy for a successful cancer treatment. However, surface functionalization involves complex procedures that increase costs and timelines, presenting challenges for clinical implementation. Biomimetic nanoparticles (BNPs) have
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Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Ying Xie, Yu Huang, Zhi-Yong Li, Weihua Jiang, Nan-Xi Shi, Yuanzhi Lu, Guangchao Cao, Zhinan Yin, Xue-Jia Lin
Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry
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ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Juan Zhang, Fan Ouyang, Anbo Gao, Tian Zeng, Ming Li, Hui Li, Wenchao Zhou, Qing Gao, Xing Tang, Qunfeng Zhang, Xiaomin Ran, Gang Tian, Xiyun Quan, Zhenzi Tang, Juan Zou, Yifei Zeng, Yunzhu Long, Yukun Li
The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. Liquid chromatography
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Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells Mol. Cancer (IF 37.3) Pub Date : 2024-05-08 Lisa-Marie Rieckmann, Michael Spohn, Lisa Ruff, David Agorku, Lisa Becker, Alina Borchers, Jenny Krause, Roisin O’Reilly, Jurek Hille, Janna-Lisa Velthaus-Rusik, Niklas Beumer, Armin Günther, Lena Willnow, Charles D. Imbusch, Peter Iglauer, Ronald Simon, Sören Franzenburg, Hauke Winter, Michael Thomas, Carsten Bokemeyer, Nicola Gagliani, Christian F. Krebs, Martin Sprick, Olaf Hardt, Sabine Riethdorf
Circulating tumor cells (CTCs) hold immense promise for unraveling tumor heterogeneity and understanding treatment resistance. However, conventional methods, especially in cancers like non-small cell lung cancer (NSCLC), often yield low CTC numbers, hindering comprehensive analyses. This study addresses this limitation by employing diagnostic leukapheresis (DLA) to cancer patients, enabling the screening
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Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer Mol. Cancer (IF 37.3) Pub Date : 2024-05-07 Moumita Kundu, Ramesh Butti, Venketesh K. Panda, Diksha Malhotra, Sumit Das, Tandrima Mitra, Prachi Kapse, Suresh W. Gosavi, Gopal C. Kundu
Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response
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circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC) Mol. Cancer (IF 37.3) Pub Date : 2024-05-07 Yi-fang Tang, Zheng-hua Liu, Lei-yi Zhang, Sheng-hao Shi, Shun Xu, Jin-An Ma, Chun-Hong Hu, Fang-wen Zou
Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired
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Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma Mol. Cancer (IF 37.3) Pub Date : 2024-05-06 Fei Li, Wenzhe Si, Li Xia, Deshan Yin, Tianjiao Wei, Ming Tao, Xiaona Cui, Jin Yang, Tianpei Hong, Rui Wei
Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. However, the role of histone lactylation in PDAC remains unclear. The level of histone lactylation in PDAC was identified by western
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Ferroptotic therapy in cancer: benefits, side effects, and risks Mol. Cancer (IF 37.3) Pub Date : 2024-05-03 Jiandong Diao, Yuanyuan Jia, Enyong Dai, Jiao Liu, Rui Kang, Daolin Tang, Leng Han, Yingjie Zhong, Lingjun Meng
Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various
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Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options Mol. Cancer (IF 37.3) Pub Date : 2024-05-03 Hongli Gao, Zhuo Xi, Jingwei Dai, Jinqi Xue, Xin Guan, Liang Zhao, Zhiguang Chen, Fei Xing
Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities
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Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications Mol. Cancer (IF 37.3) Pub Date : 2024-05-03 Joo Kyung Park, Hyoung-oh Jeong, Hyemin Kim, Jin Ho Choi, Eun Mi Lee, Seunghoon Kim, Jinho Jang, David Whee-Young Choi, Se-Hoon Lee, Kyoung Mee Kim, Kee-Taek Jang, Kwang Hyuck Lee, Kyu Taek Lee, Min Woo Lee, Jong Kyun Lee, Semin Lee
Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary
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Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance Mol. Cancer (IF 37.3) Pub Date : 2024-04-29 Jianfeng Cui, Xiaochen Liu, Qinghong Shang, Shuna Sun, Shouzhen Chen, Jianping Dong, Yaofeng Zhu, Lei Liu, Yangyang Xia, Yong Wang, Lu Xiang, Bowen Fan, Jiafeng Zhan, Yadi Zhou, Pengxiang Chen, Renchang Zhao, Xiaofei Liu, Nianzeng Xing, Dalei Wu, Benkang Shi, Yongxin Zou
CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein
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Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates Mol. Cancer (IF 37.3) Pub Date : 2024-04-27 Junqi Kuang, Pengli Li, Ziwei Zhai, Yixin Fan, HuaiYuan Xu, Chengchen Zhao, Wei Li, Xiaoxi Li, Zechuan Liang, Tao Huang, Yue Qin, Huiru Gao, Zhaoyi Ma, Dong Liu, Guifa Zhong, Bo Wang, Jing Liu, Jin Wang, Micky D. Tortorella, Baojian Liao, Duanqing Pei
Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates
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R-loop and diseases: the cell cycle matters Mol. Cancer (IF 37.3) Pub Date : 2024-04-27 Yuqin Xu, Yue Jiao, Chengbin Liu, Rui Miao, Chunyan Liu, Yilong Wang, Chunming Ma, Jiao Liu
The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop
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The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis Mol. Cancer (IF 37.3) Pub Date : 2024-04-25 Pei Yu, Yubao Han, Lulu Meng, Zengying Tang, Zhiwei Jin, Zhenzhen Zhang, Yunjiang Zhou, Jun Luo, Jianguang Luo, Chao Han, Chao Zhang, Lingyi Kong
Triple-negative breast cancer (TNBC) stands as the breast cancer subtype with the highest recurrence and mortality rates, with the lungs being the common site of metastasis. The pulmonary microenvironment plays a pivotal role in the colonization of disseminated tumor cells. Herein, this study highlights the crucial role of exosomal LAP-TGF-β1, the principal form of exosomal TGF-β1, in reshaping the
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Mutation of neurotrophic tyrosine receptor kinase can promote pan-cancer immunity and the efficacy of immunotherapy Mol. Cancer (IF 37.3) Pub Date : 2024-04-25 Congren Wang, Yingying Li, Jinyuan Huang, Huimeng Yan, Bin Zhao
The Neurotrophic tyrosine receptor kinase (NTRK) family plays important roles in tumor progression and is involved in tumor immunogenicity. Here, we conducted a comprehensive bioinformatic and clinical analysis to investigate the characteristics of NTRK mutations and their association with the outcomes in pan-cancer immunotherapy. In 3888 patients across 12 cancer types, patients with NTRK-mutant tumors
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Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-24 Yutao Li, Amit Sharma, Ingo G.H. Schmidt-Wolf
Undeniably, cancer immunotherapies have expanded the spectrum of cancer treatment, however, some patients do not respond to immunotherapies. This scenario is no different for lung cancer, whose two main types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), still pose a serious clinical challenge. Adoptive T-cell therapies (ATC), which primarily include cytokine-induced killer
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Co-transcriptional R-loops-mediated epigenetic regulation drives growth retardation and docetaxel chemosensitivity enhancement in advanced prostate cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-24 Yufan Ying, Yuqing Wu, Fenghao Zhang, Yijie Tang, Jiahe Yi, Xueyou Ma, Jiangfeng Li, Danni Chen, Xiao Wang, Xiaoyan Liu, Ben Liu, Jindan Luo, Xiangyi Zheng, Liping Xie
R-loops are prevalent three-stranded nucleic acid structures, comprising a DNA-RNA hybrid and a displaced single-stranded DNA, that frequently form during transcription and may be attributed to genomic stability and gene expression regulation. It was recently discovered that RNA modification contributes to maintain the stability of R-loops such as N6-methyladenosine (m6A). Yet, m6A-modified R-loops
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Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation Mol. Cancer (IF 37.3) Pub Date : 2024-04-20 Ander Puyalto, María Rodríguez-Remírez, Inés López, Irati Macaya, Elizabeth Guruceaga, María Olmedo, Anna Vilalta-Lacarra, Connor Welch, Sergio Sandiego, Silvestre Vicent, Karmele Valencia, Alfonso Calvo, Ruben Pio, Luis E. Raez, Christian Rolfo, Daniel Ajona, Ignacio Gil-Bazo
The identification of novel therapeutic strategies to overcome resistance to the MEK inhibitor trametinib in mutant KRAS lung adenocarcinoma (LUAD) is a challenge. This study analyzes the effects of trametinib on Id1 protein, a key factor involved in the KRAS oncogenic pathway, and investigates the role of Id1 in the acquired resistance to trametinib as well as the synergistic anticancer effect of
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Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison Mol. Cancer (IF 37.3) Pub Date : 2024-04-16 Linyan Cheng, Lujun Chen, Yuan Shi, Weiying Gu, Weidong Ding, Xiao Zheng, Yan Liu, Jingting Jiang, Zhuojun Zheng
Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy
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tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application Mol. Cancer (IF 37.3) Pub Date : 2024-04-15 Manli Zhou, Xiaoyun He, Jing Zhang, Cheng Mei, Baiyun Zhong, Chunlin Ou
Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent
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Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application Mol. Cancer (IF 37.3) Pub Date : 2024-04-06 Yuyuan Zhang, Mengjun Xu, Yuqing Ren, Yuhao Ba, Shutong Liu, Anning Zuo, Hui Xu, Siyuan Weng, Xinwei Han, Zaoqu Liu
Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes
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Loss of lncRNA LINC01056 leads to sorafenib resistance in HCC Mol. Cancer (IF 37.3) Pub Date : 2024-04-06 Yau-Tuen Chan, Junyu Wu, Yuanjun Lu, Qiucheng Li, Zixin Feng, Lin Xu, Hongchao Yuan, Tingyuan Xing, Cheng Zhang, Hor-Yue Tan, Yibin Feng, Ning Wang
Sorafenib is a major nonsurgical option for patients with advanced hepatocellular carcinoma (HCC); however, its clinical efficacy is largely undermined by the acquisition of resistance. The aim of this study was to identify the key lncRNA involved in the regulation of the sorafenib response in HCC. A clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)
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Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies Mol. Cancer (IF 37.3) Pub Date : 2024-04-05 Minghua Xiang, Huayi Li, Yuanyuan Zhan, Ding Ma, Qinglei Gao, Yong Fang
T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed
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Cancer immunometabolism: advent, challenges, and perspective Mol. Cancer (IF 37.3) Pub Date : 2024-04-05 Qin Dang, Borui Li, Bing Jin, Zeng Ye, Xin Lou, Ting Wang, Yan Wang, Xuan Pan, Qiangsheng Hu, Zheng Li, Shunrong Ji, Chenjie Zhou, Xianjun Yu, Yi Qin, Xiaowu Xu
For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the
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Crosstalk between metabolism and cell death in tumorigenesis Mol. Cancer (IF 37.3) Pub Date : 2024-04-04 Shichao Yang, Caden Hu, Xiaomei Chen, Yi Tang, Juanjuan Li, Hanqing Yang, Yi Yang, Binwu Ying, Xue Xiao, Shang‑Ze Li, Li Gu, Yahui Zhu
It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for
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Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation Mol. Cancer (IF 37.3) Pub Date : 2024-04-04 Dan Zhang, Jian-Wei Zhang, Hui Xu, Xin Chen, Yu Gao, Huan-Gang Jiang, You Wang, Han Wu, Lei Yang, Wen-Bo Wang, Jing Dai, Ling Xia, Jin Peng, Fu-Xiang Zhou
Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential
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Correction: CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-02 Hongbao Yang, Xiaobo Li, Qingtao Meng, Hao Sun, Shenshen Wu, Weiwei Hu, Guilai Liu, Xianjing Li, Yong Yang, Rui Chen
Correction: Mol Cancer 19, 13 (2020) https://doi.org/10.1186/s12943-020-1139-3 The authors are writing to request correction to the following paper published in Molecular Cancer [1]. They found Fig. 4D appeared incorrectly, as errors were introduced during preparation of these figures. They thus replace Fig. 4D at 7 days with the correct image, as follow: Corrected Fig. 4D: In addition, the sequence
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The senescence journey in cancer immunoediting Mol. Cancer (IF 37.3) Pub Date : 2024-04-01 Alessandra Zingoni, Fabrizio Antonangeli, Silvano Sozzani, Angela Santoni, Marco Cippitelli, Alessandra Soriani
Cancer progression is continuously controlled by the immune system which can identify and destroy nascent tumor cells or inhibit metastatic spreading. However, the immune system and its deregulated activity in the tumor microenvironment can also promote tumor progression favoring the outgrowth of cancers capable of escaping immune control, in a process termed cancer immunoediting. This process, which
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Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer Mol. Cancer (IF 37.3) Pub Date : 2024-04-01 Danyang Zhong, Ziyuan Wang, Zhichao Ye, Yifan Wang, Xiujun Cai
Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by
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Drug resistance in ovarian cancer: from mechanism to clinical trial Mol. Cancer (IF 37.3) Pub Date : 2024-03-28 Ling Wang, Xin Wang, Xueping Zhu, Lin Zhong, Qingxiu Jiang, Ya Wang, Qin Tang, Qiaoling Li, Cong Zhang, Haixia Wang, Dongling Zou
Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical
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Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway Mol. Cancer (IF 37.3) Pub Date : 2024-03-27 Zhiqiang He, Yuhan Zhong, Parbatraj Regmi, Tianrun Lv, Wenjie Ma, Junke Wang, Fei Liu, Siqi Yang, Yanjie Zhong, Rongxing Zhou, Yanwen Jin, Nansheng Cheng, Yujun Shi, Haijie Hu, Fuyu Li
Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. LncRNA sequencing was performed to identify the
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RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study Mol. Cancer (IF 37.3) Pub Date : 2024-03-26 Blessie Elizabeth Nelson, Jason Roszik, Jibran Ahmed, Carmelia Maria Noia Barretto, Mirella Nardo, Erick Campbell, Amber M Johnson, Sarina A. Piha-Paul, Isabella C. Glitza Oliva, Shiao-Pei Weathers, Maria Cabanillas, Milind Javle, Funda Meric-Bernstam, Vivek Subbiah
Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results
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rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC Mol. Cancer (IF 37.3) Pub Date : 2024-03-25 Giovanna Polcaro, Luigi Liguori, Valentina Manzo, Annalisa Chianese, Giuliana Donadio, Alessandro Caputo, Giosuè Scognamiglio, Federica Dell’Annunziata, Maddalena Langella, Graziamaria Corbi, Alessandro Ottaiano, Marco Cascella, Francesco Perri, Margot De Marco, Jessica Dal Col, Giovanni Nassa, Giorgio Giurato, Pio Zeppa, Amelia Filippelli, Gianluigi Franci, Fabrizio Dal Piaz, Valeria Conti, Stefano
Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs
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A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers Mol. Cancer (IF 37.3) Pub Date : 2024-03-23 Kaifeng Liu, Meijia Li, Yudong Li, Yutong Li, Zixin Chen, Yiqi Tang, Meitian Yang, Guoquan Deng, Hongwei Liu
While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared
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An international phase II trial and immune profiling of SBRT and atezolizumab in advanced pretreated colorectal cancer Mol. Cancer (IF 37.3) Pub Date : 2024-03-23 Antonin Levy, Daphné Morel, Matthieu Texier, Roger Sun, Jerome Durand-Labrunie, Maria E Rodriguez-Ruiz, Severine Racadot, Stéphane Supiot, Nicolas Magné, Stacy Cyrille, Guillaume Louvel, Christophe Massard, Loic Verlingue, Fanny Bouquet, Alberto Bustillos, Lisa Bouarroudj, Clément Quevrin, Céline Clémenson, Michele Mondini, Lydia Meziani, Lambros Tselikas, Rastilav Bahleda, Antoine Hollebecque, Eric
Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients. Eligible patients received atezolizumab 1200 mg
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LINC00115 promotes chemoresistant breast cancer stem-like cell stemness and metastasis through SETDB1/PLK3/HIF1α signaling Mol. Cancer (IF 37.3) Pub Date : 2024-03-22 Fei Luo, Mingda Zhang, Bowen Sun, Chenxin Xu, Yi Yang, Yingwen Zhang, Shanshan Li, Guoyu Chen, Ceshi Chen, Yanxin Li, Haizhong Feng
Cancer stem-like cell is a key barrier for therapeutic resistance and metastasis in various cancers, including breast cancer, yet the underlying mechanisms are still elusive. Through a genome-wide lncRNA expression profiling, we identified that LINC00115 is robustly upregulated in chemoresistant breast cancer stem-like cells (BCSCs). LncRNA microarray assay was performed to document abundance changes
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CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib Mol. Cancer (IF 37.3) Pub Date : 2024-03-21 Haosheng Li, Haoran Feng, Tao Zhang, Junwei Wu, Xiaonan Shen, Shuiyu Xu, Lianghui Xu, Shaodong Wang, Yaqi Zhang, Wenqing Jia, Xiaopin Ji, Xi Cheng, Ren Zhao
Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific
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CTLs heterogeneity and plasticity: implications for cancer immunotherapy Mol. Cancer (IF 37.3) Pub Date : 2024-03-21 Shengkun Peng, Anqi Lin, Aimin Jiang, Cangang Zhang, Jian Zhang, Quan Cheng, Peng Luo, Yifeng Bai
Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic
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Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial Mol. Cancer (IF 37.3) Pub Date : 2024-03-19 Junlong Wu, Yuda Lin, Kaiwei Yang, Xiao Liu, Huina Wang, Tingting Yu, Ran Tao, Jing Guo, Libin Chen, Huanqing Cheng, Feng Lou, Shanbo Cao, Wei Yu, Hailong Hu, Dingwei Ye
Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2
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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