-
PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives Mol. Cancer (IF 27.7) Pub Date : 2024-07-16 Zhaoyang Zhu, Yigang Jin, Jing Zhou, Fei Chen, Minjie Chen, Zhaofeng Gao, Lingyu Hu, Jinyan Xuan, Xiaoping Li, Zhengwei Song, Xiao Guo
The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors
-
Clinical application of liquid biopsy in colorectal cancer: detection, prediction, and treatment monitoring Mol. Cancer (IF 27.7) Pub Date : 2024-07-16 Xiang-Yuan Tao, Qian-Qian Li, Yong Zeng
Colorectal cancer (CRC) is one of the most prevalent malignancies affecting the gastrointestinal tract and is ranked third among cancers with the highest incidence and second-highest mortality rate worldwide. CRC exhibits a slow progression providing a wide treatment window. The currently employed CRC screening methods have shown great potential to prevent CRC and reduce CRC-related morbidity and mortality
-
Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the “Smart” exosome nanoparticle therapy Mol. Cancer (IF 27.7) Pub Date : 2024-07-15 Xin Wu, Chunmei Ban, Woding Deng, Xuewei Bao, Ning Tang, Yupeng Wu, Zhixuan Deng, Jianbin Xiong, Qiangqiang Zhao
Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into
-
ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway Mol. Cancer (IF 27.7) Pub Date : 2024-07-11 Yang Ji, Chuangye Ni, Yanjun Shen, Zhenggang Xu, Lei Tang, Fei Yu, Lingbang Zhu, Hao Lu, Chuanyong Zhang, Shikun Yang, Xuehao Wang
Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular
-
Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer Mol. Cancer (IF 27.7) Pub Date : 2024-07-10 Claudia Cifuentes, Clara L. Oeste, Isabel Fernández-Pisonero, Alejandro M. Hortal, Carmen García-Macías, Jeanne Hochart, Regina Rubira, Lydia Horndler, Carlos Horndler, Xosé R. Bustelo, Balbino Alarcón
Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene
-
A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression Mol. Cancer (IF 27.7) Pub Date : 2024-07-09 Weiwei Liu, Zhao Ding, Ye Tao, Shixian Liu, Maoyu Jiang, Fangzheng Yi, Zixi Wang, Yanxun Han, Huaiyuan Zong, Dapeng Li, Yue Zhu, Zihui Xie, Shujia Sang, Xixi Chen, Manli Miao, Xu Chen, Wei Lin, Yi Zhao, Guibin Zheng, Mark Zafereo, Guojun Li, Jing Wu, Xiaojun Zha, Yehai Liu
The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues
-
Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer Mol. Cancer (IF 27.7) Pub Date : 2024-07-09 Yifan Fu, Jinxin Tao, Tao Liu, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Zhe Cao, Guihu Weng, Taiping Zhang, Yupei Zhao
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has
-
NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer Mol. Cancer (IF 27.7) Pub Date : 2024-07-05 Min Yu, Mengdong Ni, Fei Xu, Chaohua Liu, Lihua Chen, Jiana Li, Siyu Xia, Yixin Diao, Jiaxin Chen, Jun Zhu, Xiaohua Wu, Min Tang, Jiajia Li, Guihao Ke
Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. The abundance of RNA modification in radiotherapy-resistant and sensitive
-
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients Mol. Cancer (IF 27.7) Pub Date : 2024-07-05 Lenka Hovorkova, Lucie Winkowska, Justina Skorepova, Manuela Krumbholz, Adela Benesova, Vaclava Polivkova, Julia Alten, Michela Bardini, Claus Meyer, Rathana Kim, Toby N. Trahair, Emmanuelle Clappier, Sabina Chiaretti, Michelle Henderson, Rosemary Sutton, Lucie Sramkova, Jan Stary, Katerina Machova Polakova, Rolf Marschalek, Markus Metzler, Giovanni Cazzaniga, Gunnar Cario, Jan Trka, Marketa Zaliova
The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively. By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children
-
Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy Mol. Cancer (IF 27.7) Pub Date : 2024-07-05 Bufu Tang, Jinyu Zhu, Yueli Shi, Yajie Wang, Xiaojie Zhang, Biao Chen, Shiji Fang, Yang Yang, Liyun Zheng, Rongfang Qiu, Qiaoyou Weng, Min Xu, Zhongwei Zhao, Jianfei Tu, Minjiang Chen, Jiansong Ji
The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying
-
Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma Mol. Cancer (IF 27.7) Pub Date : 2024-07-04 Byung-Sun Park, Heeju Jeon, Yeonseo Kim, Haejin Kwon, Ga-Eun Choi, Sung-Gil Chi, Hyun-Mee Park, Hyunbeom Lee, Tackhoon Kim
BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance compromises their therapeutic efficacy. Diverse genomic and transcriptomic alterations are found in BRAF inhibitor resistant melanoma, posing a pressing need for convergent, druggable target that reverse therapy resistant tumor with different resistance mechanisms. CRISPR-Cas9
-
Insights into the structural and functional activities of forgotten Kinases: PCTAIREs CDKs Mol. Cancer (IF 27.7) Pub Date : 2024-06-29 Javad Karimbayli, Ilenia Pellarin, Barbara Belletti, Gustavo Baldassarre
In cells, signal transduction heavily relies on the intricate regulation of protein kinases, which provide the fundamental framework for modulating most signaling pathways. Dysregulation of kinase activity has been implicated in numerous pathological conditions, particularly in cancer. The druggable nature of most kinases positions them into a focal point during the process of drug development. However
-
Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications Mol. Cancer (IF 27.7) Pub Date : 2024-06-29 Chaohua Si, Jianen Gao, Xu Ma
Natural killer (NK) cells are important immune cells in the organism and are the third major type of lymphocytes besides T cells and B cells, which play an important function in cancer therapy. In addition to retaining the tumor cell killing function of natural killer cells, natural killer cell-derived exosomes cells also have the characteristics of high safety, wide source, easy to preserve and transport
-
Serum small RNAs in metastatic colorectal cancer predict response to chemotherapy and characterize high-risk patients Mol. Cancer (IF 27.7) Pub Date : 2024-06-27 Robin Mjelle, Are K. Kristensen, Tora S. Solheim, Ganna S. Westvik, Hege Elvebakken, Eva Hofsli
Metastatic colorectal cancer (mCRC) presents significant challenges in clinical management due to its heterogeneity and variable response to treatment. In this study, we conducted comprehensive small RNA (sRNA) sequencing analyses to identify sRNA biomarkers associated with survival and treatment response in mCRC patients. We measured serum sRNAs before and after chemotherapy treatment in a discovery
-
Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma Mol. Cancer (IF 27.7) Pub Date : 2024-06-26 Junjie Zhao, Yanfeng Tang, Xu Hu, Xiaoxue Yin, Yuntian Chen, Junru Chen, Haoyang Liu, Haolin Liu, Jiayu Liang, Xingming Zhang, Jinge Zhao, Sha Zhu, Yuchao Ni, Zhipeng Wang, Jindong Dai, Zilin Wang, Yaowen Zhang, Jin Yao, Ni Chen, Pengfei Shen, Zhenhua H. Liu, Hao Zeng, Guangxi X. Sun
TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included
-
Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond Mol. Cancer (IF 27.7) Pub Date : 2024-06-26 Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains
-
The role of RNA methylation in tumor immunity and its potential in immunotherapy Mol. Cancer (IF 27.7) Pub Date : 2024-06-20 Yan Li, Haoer Jin, Qingling Li, Liangrong Shi, Yitao Mao, Luqing Zhao
RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating RNA splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of RNA methylation on tumor immunity. The primary types of RNA methylation encompass N6-methyladenosine
-
Advances in spatial transcriptomics and its applications in cancer research Mol. Cancer (IF 27.7) Pub Date : 2024-06-20 Yang Jin, Yuanli Zuo, Gang Li, Wenrong Liu, Yitong Pan, Ting Fan, Xin Fu, Xiaojun Yao, Yong Peng
Malignant tumors have increasing morbidity and high mortality, and their occurrence and development is a complicate process. The development of sequencing technologies enabled us to gain a better understanding of the underlying genetic and molecular mechanisms in tumors. In recent years, the spatial transcriptomics sequencing technologies have been developed rapidly and allow the quantification and
-
Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis Mol. Cancer (IF 27.7) Pub Date : 2024-06-18 Maoye Wang, Xiaoge Ding, Xinjian Fang, Jing Xu, Yanke Chen, Yu Qian, Jiahui Zhang, Dan Yu, Xiaoxin Zhang, Xiuqin Ma, Taofeng Zhu, Jianmei Gu, Xu Zhang
Circular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear. In this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally
-
Multi-omics profiling reveal cells with novel oncogenic cluster, TRAP1low/CAMSAP3low, emerge more aggressive behavior and poor-prognosis in early-stage endometrial cancer Mol. Cancer (IF 27.7) Pub Date : 2024-06-17 Xiaodan Mao, Xiaoyue Tang, Jingxuan Ye, Shuxia Xu, Yue Wang, Xianhua Liu, Qibin Wu, Xite Lin, Maotong Zhang, Jiangfeng Liu, Juntao Yang, Pengming Sun
The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous
-
Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations Mol. Cancer (IF 27.7) Pub Date : 2024-06-11 Syuzo Kaneko, Ken Takasawa, Ken Asada, Kouya Shiraishi, Noriko Ikawa, Hidenori Machino, Norio Shinkai, Maiko Matsuda, Mari Masuda, Shungo Adachi, Satoshi Takahashi, Kazuma Kobayashi, Nobuji Kouno, Amina Bolatkan, Masaaki Komatsu, Masayoshi Yamada, Mototaka Miyake, Hirokazu Watanabe, Akiko Tateishi, Takaaki Mizuno, Yu Okubo, Masami Mukai, Tatsuya Yoshida, Yukihiro Yoshida, Hidehito Horinouchi, Shun-Ichi
In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case. Despite this, most cancer research has approached the analysis of these data sets separately
-
Cell surface CD55 traffics to the nucleus leading to cisplatin resistance and stemness by inducing PRC2 and H3K27 trimethylation on chromatin in ovarian cancer Mol. Cancer (IF 27.7) Pub Date : 2024-06-10 Rashmi Bharti, Goutam Dey, Debjit Khan, Alex Myers, Olivia G. Huffman, Caner Saygin, Chad Braley, Elliott Richards, Naseer Sangwan, Belinda Willard, Justin D. Lathia, Paul L. Fox, Feng Lin, Babal Kant Jha, J. Mark Brown, Jennifer S. Yu, Mohammed Dwidar, Amy Joehlin-Price, Roberto Vargas, Chad M. Michener, Michelle S. Longworth, Ofer Reizes
Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and
-
Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer Mol. Cancer (IF 27.7) Pub Date : 2024-06-08 Yiran Liang, Fangzhou Ye, Dan Luo, Li Long, Yajie Wang, Yuhan Jin, Lei Wang, Yaming Li, Dianwen Han, Bing Chen, Wenjing Zhao, Lijuan Wang, Qifeng Yang
Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated
-
OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway Mol. Cancer (IF 27.7) Pub Date : 2024-06-07 Hongfa Wei, Wenchao Li, Leli Zeng, Ni Ding, Kuan Li, Hong Yu, Fei Jiang, Haofan Yin, Yu Xia, Cuncan Deng, Nan Cai, Xiancong Chen, Liang Gu, Huanjie Chen, Feiran Zhang, Yulong He, Jia Li, Changhua Zhang
Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric
-
Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy Mol. Cancer (IF 27.7) Pub Date : 2024-06-07 Marc Zuckermann, Chen He, Jared Andrews, Aditi Bagchi, Roketa Sloan-Henry, Brandon Bianski, Jia Xie, Yingzhe Wang, Nathaniel Twarog, Arzu Onar-Thomas, Kati J. Ernst, Lei Yang, Yong Li, Xiaoyan Zhu, Jennifer K. Ocasio, Kaitlin M. Budd, James Dalton, Xiaoyu Li, Divyabharathi Chepyala, Junyuan Zhang, Ke Xu, Laura Hover, Jordan T. Roach, Kenneth Chun-Ho Chan, Nina Hofmann, Peter J. McKinnon, Stefan M.
Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. To identify new treatment options, we established and characterized
-
Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets Mol. Cancer (IF 27.7) Pub Date : 2024-06-07 Shenglan Liu, Wei Dai, Bei Jin, Feng Jiang, Hao Huang, Wen Hou, Jinxia Lan, Yanli Jin, Weijie Peng, Jingxuan Pan
Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which
-
Diversifying the anthracycline class of anti-cancer drugs identifies aclarubicin for superior survival of acute myeloid leukemia patients Mol. Cancer (IF 27.7) Pub Date : 2024-06-04 Xiaohang Qiao, Sabina Y. van der Zanden, Xiaoyang Li, Minkang Tan, Yunxiang Zhang, Ji-Ying Song, Merle A. van Gelder, Feija L. Hamoen, Lennert Janssen, Charlotte L. Zuur, Baoxu Pang, Olaf van Tellingen, Junmin Li, Jacques Neefjes
The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet
-
Correction: Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma Mol. Cancer (IF 27.7) Pub Date : 2024-06-03 Weiwei Liu, Lu zheng, Rongguiyi Zhang, Ping Hou, Jiakun Wang, Linquan Wu, Jing Li
Correction to: Mol Cancer 21, 72(2022) https://doi.org/10.1186/s12943-022-01529-5 After the original article was published [1], The author found a typo in the subscript of the X-axis in Fig. 1B, i.e., Toumor should be in the Normal position. And in Fig. 3C the image in ShNC was used incorrectly. Therefore, the authors want to update it to the correct figures. The other elements in the figure remain
-
Genome-wide in vivo CRISPR screen identifies TGFβ3 as actionable biomarker of palbociclib resistance in triple negative breast cancer Mol. Cancer (IF 27.7) Pub Date : 2024-06-03 Sophie Poulet, Meiou Dai, Ni Wang, Gang Yan, Julien Boudreault, Girija Daliah, Alan Guillevin, Huong Nguyen, Soaad Galal, Suhad Ali, Jean-Jacques Lebrun
Triple negative breast cancer (TNBC) remains exceptionally challenging to treat. While CDK4/6 inhibitors have revolutionized HR + breast cancer therapy, there is limited understanding of their efficacy in TNBC and meaningful predictors of response and resistance to these drugs remain scarce. We conducted an in vivo genome-wide CRISPR screen using palbociclib as a selection pressure in TNBC. Hits were
-
A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy Mol. Cancer (IF 27.7) Pub Date : 2024-06-01 Na Li, Shinan Geng, Zhen-zhen Dong, Ying Jin, Hangjie Ying, Hung-Wing Li, Liyun Shi
Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors
-
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2 Mol. Cancer (IF 27.7) Pub Date : 2024-05-31 Diguang Wen, Hang Xiao, Yueyi Gao, Hanqing Zeng, Jianchuan Deng
Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear. We evaluated the expression pattern of SENP1 based on RNA sequencing data obtained from OHSU, TCGA, TARGET, and MILE datasets. Clinical samples were used to verify the expression of SENP1 in the AML cells. Lentiviral vectors shRNA and sgRNA were used to intervene
-
Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study Mol. Cancer (IF 27.7) Pub Date : 2024-05-30 Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O’Brien, Luis Paz-Ares, Jonathan W. Goldman, Marina Chiara Garassino, Carl M. Gay, John V. Heymach, Haiyi Jiang, J. Carl Barrett, Ross A. Stewart, Zhongwu Lai, Lauren A. Byers, Charles M. Rudin, Yashaswi Shrestha
We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial. 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall
-
JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression Mol. Cancer (IF 27.7) Pub Date : 2024-05-29 Torben Redmer, Martin Raigel, Christina Sternberg, Roman Ziegler, Clara Probst, Desiree Lindner, Astrid Aufinger, Tanja Limberger, Karolina Trachtova, Petra Kodajova, Sandra Högler, Michaela Schlederer, Stefan Stoiber, Monika Oberhuber, Marco Bolis, Heidi A. Neubauer, Sara Miranda, Martina Tomberger, Nora S. Harbusch, Ines Garces de los Fayos Alonso, Felix Sternberg, Richard Moriggl, Jean-Philippe
Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood. We analyzed JUN expression in clinical prostate cancer samples across
-
CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis Mol. Cancer (IF 27.7) Pub Date : 2024-05-28 Xiao-Yu Zhang, Shan-Shan Li, Yu-Rong Gu, Le-Xin Xiao, Xin-Yi Ma, Xin-Ru Chen, Jia-Liang Wang, Chun-Hong Liao, Bing-Liang Lin, Yue-Hua Huang, Yi-Fan Lian
The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. Functional analyses were conducted to assess circPIAS1’s impact on HCC cell proliferation, migration
-
Correction: Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2 Mol. Cancer (IF 27.7) Pub Date : 2024-05-25 Yuchun Niu, Feng Ma, Weimei Huang, Shun Fang, Man Li, Ting Wei, Linlang Guo
Correction: Mol Cancer16, 5 (2017) https://doi.org/10.1186/s12943-016-0575-6 Following publication of the original article [1], the authors noticed that two images (Figs. 2E and 5C) in the plate clone experiment section were accidentally duplicated due to personal negligence. They fully understand that this mistake may have caused inconvenience to the readers and raised doubts about the rigor of their
-
PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer Mol. Cancer (IF 27.7) Pub Date : 2024-05-22 Chaohua Liu, Jiana Li, Fei Xu, Lihua Chen, Mengdong Ni, Jiangchun Wu, Haiyun Zhao, Yangjun Wu, Jiajia Li, Xiaohua Wu, Xiaojun Chen
Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. This study analyzed the expression of DOT1L in PARPi-resistant
-
New-generation advanced PROTACs as potential therapeutic agents in cancer therapy Mol. Cancer (IF 27.7) Pub Date : 2024-05-21 Chao Wang, Yujing Zhang, Wujun Chen, Yudong Wu, Dongming Xing
Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs)
-
KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges Mol. Cancer (IF 27.7) Pub Date : 2024-05-20 Chang-Yun Li, Wanhe Wang, Chung-Hang Leung, Guan-Jun Yang, Jiong Chen
Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations
-
Regulatory mechanisms of PD-1/PD-L1 in cancers Mol. Cancer (IF 27.7) Pub Date : 2024-05-18 Xin Lin, Kuan Kang, Pan Chen, Zhaoyang Zeng, Guiyuan Li, Wei Xiong, Mei Yi, Bo Xiang
Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response
-
Neutrophils in Cancer immunotherapy: friends or foes? Mol. Cancer (IF 27.7) Pub Date : 2024-05-18 Xueqin Huang, Eugenie Nepovimova, Vojtech Adam, Ladislav Sivak, Zbynek Heger, Marian Valko, Qinghua Wu, Kamil Kuca
Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity
-
Aging and cancer Mol. Cancer (IF 27.7) Pub Date : 2024-05-18 Léa Montégut, Carlos López-Otín, Guido Kroemer
Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time, irrespective of the precise causes, can be confronted with the idea that aging and cancer share common mechanistic grounds that are referred to as ‘hallmarks’. Indeed, several hallmarks of aging also contribute to carcinogenesis and tumor progression
-
RICTOR/mTORC2 downregulation in BRAFV600E melanoma cells promotes resistance to BRAF/MEK inhibition Mol. Cancer (IF 27.7) Pub Date : 2024-05-16 Luca Ponzone, Valentina Audrito, Claudia Landi, Enrico Moiso, Chiara Levra Levron, Sara Ferrua, Aurora Savino, Nicoletta Vitale, Massimiliano Gasparrini, Lidia Avalle, Lorenza Vantaggiato, Enxhi Shaba, Beatrice Tassone, Stefania Saoncella, Francesca Orso, Daniele Viavattene, Eleonora Marina, Irene Fiorilla, Giulia Burrone, Youssef Abili, Fiorella Altruda, Luca Bini, Silvia Deaglio, Paola Defilippi
The main drawback of BRAF/MEK inhibitors (BRAF/MEKi)-based targeted therapy in the management of BRAF-mutated cutaneous metastatic melanoma (MM) is the development of therapeutic resistance. We aimed to assess in this context the role of mTORC2, a signaling complex defined by the presence of the essential RICTOR subunit, regarded as an oncogenic driver in several tumor types, including MM. After analyzing
-
DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma Mol. Cancer (IF 27.7) Pub Date : 2024-05-16 Yangfan Liu, Yu Sun, Jin Yang, Deyang Wu, Shuang Yu, Junjiang Liu, Tao Hu, Jingjing Luo, Hongmei Zhou
The faithful maintenance of DNA methylation homeostasis indispensably requires DNA methyltransferase 1 (DNMT1) in cancer progression. We previously identified DNMT1 as a potential candidate target for oral squamous cell carcinoma (OSCC). However, how the DNMT1- associated global DNA methylation is exploited to regulate OSCC remains unclear. The shRNA-specific DNMT1 knockdown was employed to target
-
NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer Mol. Cancer (IF 27.7) Pub Date : 2024-05-16 Miltiadis Tsesmelis, Ulrike F. G. Büttner, Melanie Gerstenlauer, Uta Manfras, Konstantinos Tsesmelis, Ziwei Du, Nadine Sperb, Stephanie Ellen Weissinger, Peter Möller, Thomas F. E. Barth, Harald J. Maier, Lap Kwan Chan, Thomas Wirth
Pancreatic ductal adenocarcinoma (PDAC) is marked by a dismal survival rate, lacking effective therapeutics due to its aggressive growth, late-stage diagnosis, and chemotherapy resistance. Despite debates on NF-κB targeting for PDAC treatment, no successful approach has emerged. To elucidate the role of NF-κB, we ablated NF-κB essential modulator (NEMO), critical for conventional NF-κB signaling, in
-
CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation Mol. Cancer (IF 27.7) Pub Date : 2024-05-16 Yaming Li, Zekun Wang, Jingwen Yang, Yuhan Sun, Yinqiao He, Yuping Wang, Xi Chen, Yiran Liang, Ning Zhang, Xiaolong Wang, Wenjing Zhao, Guohong Hu, Qifeng Yang
Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome
-
CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair Mol. Cancer (IF 27.7) Pub Date : 2024-05-15 Lu Wang, Mainá Bitar, Xue Lu, Sebastien Jacquelin, Sneha Nair, Haran Sivakumaran, Kristine M. Hillman, Susanne Kaufmann, Rebekah Ziegman, Francesco Casciello, Harsha Gowda, Joseph Rosenbluh, Stacey L. Edwards, Juliet D. French
Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression
-
Correction: Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340 Mol. Cancer (IF 27.7) Pub Date : 2024-05-14 Xiangyu Jian, Han He, Jiehong Zhu, Qi Zhang, Zhongxin Zheng, Xiangjing Liang, Liuyan Chen, Meiling Yang, Kaiyue Peng, Zhaowen Zhang, Tengfei Liu, Yaping Ye, Hongli Jiao, Shuyang Wang, Weijie Zhou, Yanqing Ding, Tingting Li
Correction: Mol Cancer 19, 20 (2020) https://doi.org/10.1186/s12943-020-1134-8 Following publication of the original article [1], the authors would like to request for the below changes. 1. We request to replace the misused image in Fig.2H-Scramble-96h with the correct image. Figure 2H 2. We request to replace the misused images of Fig. 3I-circ001680+miR340 and 3L-ki67- circ001680+miR340 with the correct
-
Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer Mol. Cancer (IF 27.7) 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
-
Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors Mol. Cancer (IF 27.7) 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
-
DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy Mol. Cancer (IF 27.7) 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
-
Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma Mol. Cancer (IF 27.7) 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
-
Autologous patient-derived exhausted nano T-cells exploit tumor immune evasion to engage an effective cancer therapy Mol. Cancer (IF 27.7) 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
-
Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells Mol. Cancer (IF 27.7) 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
-
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 27.7) 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
-
Diagnostic leukapheresis reveals distinct phenotypes of NSCLC circulating tumor cells Mol. Cancer (IF 27.7) 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
-
Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer Mol. Cancer (IF 27.7) 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
-
circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC) Mol. Cancer (IF 27.7) 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
-
Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma Mol. Cancer (IF 27.7) 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
-
Ferroptotic therapy in cancer: benefits, side effects, and risks Mol. Cancer (IF 27.7) 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
-
Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options Mol. Cancer (IF 27.7) 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