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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
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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