Cancer Communications最新文献

{"title":"Incidence of and survival with bone and soft tissue sarcoma: A nation-wide study over four decades","authors":"Maria Anna Smolle,&nbsp;Florian Alexander Wenzl,&nbsp;Joanna Szkandera,&nbsp;Susanne Scheipl,&nbsp;Bernadette Liegl-Atzwanger,&nbsp;Jasminka Igrec,&nbsp;Andreas Leithner","doi":"10.1002/cac2.12653","DOIUrl":"10.1002/cac2.12653","url":null,"abstract":"<p>Demographic and environmental factors determine the incidence of and survival with malignancies, including sarcoma [<span>1</span>]. Accordingly, the annual incidence of soft tissue sarcomas (STS) has markedly increased since the early 2000s [<span>2, 3</span>]. Likewise, there appears to be an overall increase in the incidence of bone sarcomas (BS) since 1975 [<span>4, 5</span>]. In parallel, one study reports moderate improvement in the survival of adult patients with BS and STS up to 2007 [<span>6</span>]. Previous studies were often based on cancer registries with low coverage rates [<span>3, 7, 8</span>], focused on limited time periods [<span>3, 9, 10</span>], or did not include data from recent years [<span>3, 6</span>]. Thus, current data from high-income European countries with an advanced health care system on incidence and prognosis of sarcoma patients are scarce. Consequently, the purpose of this study was to analyse the incidence of and survival with BS and STS in the general population of Austria from 1983 to 2020. A detailed description of materials and methods is outlined in the Supplementary Materials (Supplementary Materials and Methods).</p><p>Across the 38-year observation period, 2,491 patients in Austria were diagnosed with BS (Supplementary Tables S1-S2, Supplementary Figure S1). Male-to-female ratio was 1.27, favouring males (range over the years: 0.56-1.23), which remained constant over time <i>(P =</i> 0.529; Supplementary Table S3).</p><p>Throughout the observation period, mean age-adjusted BS incidence was 0.80 per 100,000 (95% confidence interval [CI]: 0.61-0.98; Figure 1A). We observed a significant increase in incidence from 1983 to 2020, with an average annual percentage change (AAPC) of 7.2% (95%CI: 6.2%-8.5%; <i>P</i> &lt; 0.001; Supplementary Table S4). Similar results were obtained in a sensitivity analysis excluding the initial 7 years of the observation period (<i>ie</i>, 1983-1989; AAPC: 1.5% [95%CI: 1.0%-2.1%]; <i>P</i> &lt; 0.001) and chondrosarcoma diagnoses (AAPC: 5.8% [95%CI: 4.9%-7.2%]; <i>P</i> &lt; 0.001; Supplementary Figure S2A; Supplementary Table S4).</p><p>Age at diagnosis of BS followed a bimodal distribution, with peaks in incidence around the age of 15 years and 70 years (Figure 1B), both in males and females (Supplementary Figure S3A). Notably, a shift towards increased BS incidence in older age groups was present in recent years (Supplementary Figure S4A, Supplementary Figure S5A). In a sensitivity analysis excluding all chondrosarcoma diagnoses, a similar pattern was observed (Supplementary Figure S2B).</p><p>Five-year relative survival was 65.9% (95%CI: 63.9%-67.9%). No change in 5-year relative survival was found from the first time period (1987-1990; 5-year relative survival: 65.3% [95%CI: 50.7%-76.7%]) to the last time period (2015-2020; 5-year relative survival: 66.7% [95%CI: 62.5%70.7%]; <i>P</i> = 0.735; Figure 1C). Of note, the youngest age group (0-20 years) had better 5-year r","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 4","pages":"397-400"},"PeriodicalIF":20.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic and regulatory T cell interactions calculated from image mass cytometry predict immunochemotherapy response in triple-negative breast cancer","authors":"Xiang Wang,&nbsp;Jing Dong,&nbsp;Jian-Rong Li,&nbsp;Yupei Lin,&nbsp;Bikram Sahoo,&nbsp;Yong Li,&nbsp;Yanhong Liu,&nbsp;Robert Taylor Ripley,&nbsp;Jia Wu,&nbsp;Jianjun Zhang,&nbsp;Christopher I Amos,&nbsp;Chao Cheng","doi":"10.1002/cac2.12652","DOIUrl":"10.1002/cac2.12652","url":null,"abstract":"&lt;p&gt;In the tumor microenvironment (TME), various types of immune cells interact with each other and with cancer cells, playing critical roles in cancer progression and treatment [&lt;span&gt;1&lt;/span&gt;]. Numerous studies have reported that the infiltration levels of specific immune cells are associated with patient prognosis and response to immunotherapies [&lt;span&gt;2, 3&lt;/span&gt;]. For instance, the density of pre-existing tumor infiltrating lymphocytes in the TME has been found to positively correlate with patient responses to anti-PD-1 treatment in triple-negative breast cancer (TNBC) [&lt;span&gt;3&lt;/span&gt;]. However, the relationship between immune cell-cell interactions (CCIs) in the TME and patient clinical outcomes remains unclear due to the limited availability of large-scale datasets for systematic CCI investigation. Recently, imaging mass cytometry (IMC) has been utilized to characterize the immune landscape within the TME of tumor samples [&lt;span&gt;4&lt;/span&gt;]. IMC can detect 30 to 40 protein markers on a single tissue slide, enabling the visualization of spatial distributions of various cell types at single-cell resolution. Analyzing IMC data enables the quantification of interactions between all TME cell types by examining their spatial distributions.&lt;/p&gt;&lt;p&gt;In this study, we conducted a systematic analysis to investigate the association between CCIs and treatment responses of cancer patients using a large IMC dataset. The dataset comprises the immune landscape of 660 tumor samples from 279 TNBC patients enrolled in a randomized clinical trial [&lt;span&gt;4&lt;/span&gt;]. These patients were treated with either neoadjuvant chemotherapy (&lt;i&gt;n&lt;/i&gt; = 141) or immunochemotherapy therapy (chemotherapy combined with anti-PD-L1 immunotherapy, (&lt;i&gt;n&lt;/i&gt; = 138), with tumor samples collected at three time points for IMC analysis: baseline, early on-treatment, and post-treatment. We applied a modified method introduced by Windhager &lt;i&gt;et al.&lt;/i&gt; [&lt;span&gt;5&lt;/span&gt;] to quantify interactions for all pairs of cell types captured by IMC and examined their associations with patient outcomes (Supplementary Material and Methods). Our results indicated that compared to the infiltration levels of immune cells, CCIs between specific immune cell types were more strongly correlated with patient responses. Notably, we found that the interaction between regulatory T cells (Treg) and GZMB&lt;sup&gt;+&lt;/sup&gt; cytotoxic CD8&lt;sup&gt;+&lt;/sup&gt; T (Tc) cells in pre-treatment samples was predictive of patient response to immunochemotherapy but not to chemotherapy alone in TNBC.&lt;/p&gt;&lt;p&gt;The processed IMC data provides the coordinates of all single cells along with their cell type annotations. To quantify the interaction from cell type X to Y (X→Y), we calculated the average number of X cells among the 10 nearest neighbors of each Y cell and standardized this as a Z-score by comparing it with a null distribution generated through permutations. In each permutation, we shuffled the labels of all cell types except epithelial cel","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 4","pages":"392-396"},"PeriodicalIF":20.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient 5-ALA-photodynamic therapy in nasopharyngeal carcinoma induces an immunoactivation mediated by tumoral extracellular vesicles and associated with immunogenic cell death","authors":"Camille Trioën,&nbsp;Thomas Soulier,&nbsp;Jacquie Massoud,&nbsp;Clément Bouchez,&nbsp;Nicolas Stoup,&nbsp;Anthony Lefebvre,&nbsp;Anne-Sophie Dewalle,&nbsp;Guillaume Paul Grolez,&nbsp;Nadira Delhem,&nbsp;Olivier Moralès","doi":"10.1002/cac2.12656","DOIUrl":"10.1002/cac2.12656","url":null,"abstract":"&lt;p&gt;Nasopharyngeal carcinoma (NPC) is a rare cancer, with 120,334 cases worldwide in 2022, but it remains endemic in Southeast Asia and North Africa. Early-stage NPC is typically treated with radiotherapy, often combined with chemotherapy for advanced stages [&lt;span&gt;1&lt;/span&gt;]. Despite a 5-year survival rate of 70% to 90% for locoregional disease, late-stage diagnosis and locoregional or distant recurrence and metastasis (R/M) result in a poor prognosis for many patients, underscoring the urgent need for novel therapeutic strategies [&lt;span&gt;2-4&lt;/span&gt;]. The tumor microenvironment, enriched with immunosuppressive elements such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs), plays a central role in promoting immune evasion and resistance to therapy. In NPC, effective therapeutic strategies should not only induce tumor cell death but also reprogram this immunosuppressive microenvironment to restore robust anti-tumor immunity. To address these challenges, we propose evaluating the efficacy of photodynamic therapy (PDT) and its immunoactivating properties in NPC. PDT is a non-invasive treatment that induces cell death via reactive oxygen species (ROS) and activates an anti-tumor immune response by releasing tumor antigens and damage-associated molecular patterns (DAMPs) [&lt;span&gt;5, 6&lt;/span&gt;]. After examining the direct cell death induced by 5-aminolevulinic acid (5-ALA)-PDT, we investigated its ability to trigger immune activation and its effects on immune cell populations and their secretome. Lastly, we conducted an in-depth analysis of molecular and vesicular (extracellular vesicle) components to understand the mechanisms underlying immune response activation. Detailed study designs and methods are available in the Supplementary Materials.&lt;/p&gt;&lt;p&gt;The prodrug 5-ALA is preferentially absorbed by tumor cells and metabolized into protoporphyrin IX (PpIX), the photosensitizer, via the heme synthesis pathway (Supplementary Figure S1A). To evaluate 5-ALA-PDT in NPC cell lines, we assessed their capacity to convert 5-ALA into PpIX. We observed that NPC cell lines expressed key enzymes and transporters involved in the heme pathway, with no significant differences, confirming their ability to metabolize 5-ALA into PpIX (Supplementary Figure S1B). We then incubated NPC cells with varying concentrations of 5-ALA, showing successful conversion of 5-ALA into intracellular PpIX after 2 hours, followed by extracellular release of PpIX between 6 to 8 hours (Figure 1A, Supplementary Figure S1C). Based on these findings and considering clinical data, we selected a 4-hour incubation period for subsequent experiments.&lt;/p&gt;&lt;p&gt;To determine the direct impact and efficacy of 5-ALA-PDT on NPC cell lines, we subjected the cells to 5-ALA-PDT. A dose-dependent reduction in cell viability was observed, with CNE2 cells (EC50: 104.9 µmol/L) exhibiting greater sensitivity to treatment compared to CNE1 cells (EC50: 209.7 µmol/L) (Figure 1B, Suppl","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 4","pages":"401-405"},"PeriodicalIF":20.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale 3D spatial analysis of the tumor microenvironment using whole-tissue digital histopathology","authors":"Daniel Shafiee Kermany,&nbsp;Ju Young Ahn,&nbsp;Matthew Vasquez,&nbsp;Weijie Zhang,&nbsp;Lin Wang,&nbsp;Kai Liu,&nbsp;Zhan Xu,&nbsp;Min Soon Cho,&nbsp;Wendolyn Carlos-Alcalde,&nbsp;Hani Lee,&nbsp;Raksha Raghunathan,&nbsp;Jianting Sheng,&nbsp;Xiaoxin Hao,&nbsp;Hong Zhao,&nbsp;Vahid Afshar-Kharghan,&nbsp;Xiang Hong-Fei Zhang,&nbsp;Stephen Tin Chi Wong","doi":"10.1002/cac2.12655","DOIUrl":"10.1002/cac2.12655","url":null,"abstract":"<p>Spatial statistics are crucial for analyzing clustering patterns in various spaces, such as the distribution of trees in a forest or stars in the sky. Advances in spatial biology, such as single-cell spatial transcriptomics, enable researchers to map gene expression patterns within tissues, offering unprecedented insights into cellular functions and disease pathology. Common methods for deriving spatial relationships include density-based methods (quadrat analysis, kernel density estimators) and distance-based methods (nearest-neighbor distance [NND], Ripley's K function). While density-based methods are effective for visualization, they struggle with quantification due to sensitivity to parameters and complex significance tests. In contrast, distance-based methods offer robust frameworks for hypothesis testing, quantifying spatial clustering or dispersion, and facilitating comparisons with models such as uniform random distributions or Poisson processes [<span>1, 2</span>].</p><p>Ripley's K function provides a detailed measure of spatial clustering or dispersion across multiple scales by considering all pairs of points within specified distances. This is in contrast to NND, which may overlook structures that vary across scales. Ripley's K function can detect complex spatial patterns over a range of distances, making it suitable for datasets with non-uniform arrangements that exhibit different behaviors at different scales. However, its broader adoption has been hindered by computational complexity and challenges in interpretation, especially for three-dimensional data, which are common in spatial biomedical research [<span>3-6</span>].</p><p>To address these limitations, we introduce MDSpacer (Multi-Dimensional Spatial Pattern Analysis with Comparable and Extendable Ripley's K), a modeling tool that implements Ripley's K function for both 2D and 3D data, facilitating detailed analyses within and between groups (Figure 1A, B, Supplementary Figure S1). MDSpacer uses a novel normalization scheme (described in Supplementary Materials and Methods) that dramatically reduces computational overhead while delivering results in an easily interpretable and comparable format (Figure 1C–F). We validated this tool in two cancer research studies: one on metastatic bone cancer and another on ovarian cancer. In the metastatic bone cancer study, we used the Vessel3D analysis toolkit to extract spatial point information from 3D confocal images of murine femurs with early-stage spontaneous metastasis (Figure 1G–K, Supplementary Figures S2, S3, Supplementary Videos S1, S2). MDSpacer identified both expected clustering at short distances and unexpected dispersion patterns at larger scales between early-stage disseminated tumor cells (DTCs) and neural/glial antigen 2-positive (NG2⁺) mesenchymal cells in relation to other microenvironmental factors [<span>7-9</span>]. Interestingly, no spatial relationships were observed between DTCs and vessel bifurcatio","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"386-390"},"PeriodicalIF":20.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A strong internal promoter drives massive expression of YEATS-domain devoid MLLT3 transcripts in HSC and most lethal AML","authors":"Chloé Bessière,&nbsp;Ahmed Zamani,&nbsp;Romain Pfeifer,&nbsp;Sandra Dailhau,&nbsp;Camille Marchet,&nbsp;Benoit Guibert,&nbsp;Anthony Boureux,&nbsp;Raïssa Silva Da Silva,&nbsp;Nicolas Gilbert,&nbsp;Thérèse Commes,&nbsp;Fabienne Meggetto,&nbsp;Christian Touriol,&nbsp;Christian Récher,&nbsp;Marina Bousquet,&nbsp;Stéphane Pyronnet","doi":"10.1002/cac2.12650","DOIUrl":"10.1002/cac2.12650","url":null,"abstract":"<p>The AF9 (protein AF9) transcription factor, encoded by <i>MLLT3</i> (<i>mixed-lineage leukemia translocated to 3</i>) on chromosome 9, functions as a chromatin reader. Through its N-terminal YEATS (Yaf9, ENL, AF9, Taf14, and Sas5) protein domain, it interacts with acetylated [<span>1</span>] or crotonylated [<span>2</span>] histone H3, as well as with the PAF1 (RNA polymerase II-associated factor 1 homolog) and P-TEFb (positive transcription elongation factor b) components of the super elongation complex (SEC). AF9 also interacts through its poly-serine domain (Poly-Ser) with the TFIID (Transcription factor II D) subunit of the RNA polymerase II (RNApol II) complex. In addition, its C-terminal transactivation domain, AHD (nuclear anchorage protein1 homology domain), binds other SEC components, such as AFF1 and AFF4 (ALF transcription elongation factor 1 or 4), as well as transcription regulators CBX8 (chromobox 8), DOT1L (disruptor of telomeric silencing 1 like), and BCOR (B cell lymphoma 6 corepressor), as reviewed by Kabra &amp; Bushweller [<span>3</span>] (Figure 1A). Thus, MLLT3 is an integral part of the SEC, which is essential for optimizing the catalytic activity of RNApol II transcription at specific genome loci.</p><p>Several studies have indicated that <i>MLLT3</i> is highly and specifically expressed in hematopoietic stem cells (HSCs), but it is rapidly and significantly downregulated during normal differentiation or immediately after HSCs are placed in <i>ex vivo</i> culture. In both scenarios, this shutdown parallels the rapid loss of stemness. Consistently, ectopic expression of <i>MLLT3</i> significantly prolongs self-renewal capacity of HSCs, suggesting that <i>MLLT3</i> is a crucial factor for HSC maintenance [<span>4</span>].</p><p>Based on standard quantification of RNA-sequencing reads mapping to the <i>MLLT3</i> locus, we first confirmed that, compared to the <i>MLLT1</i> paralogue used as an internal control, <i>MLLT3</i> expression was significantly higher in CD34⁺ cells than in mature lymphocytes, granulocytes, or monocytes from healthy samples of the Leucegene dataset (Leucegene-NH, detailed in Supplementary Information) (Figure 1B, left panel). To refine this observation, made in CD34⁺ cells containing a mixture of progenitors but only a few HSCs, we repeated the analysis in HSCs and various stages of progenitor cells sorted form healthy donors (IUCT-NH, detailed in Supplementary Information). The data clearly confirmed that <i>MLLT3</i> is highly expressed in HSCs but rapidly declines as differentiation proceeds (Figure 1B, right panel).</p><p>However, closer examination using a k-mer approach (described in Materials and Methods in Supplementary Information), which visualized RNA-sequencing read alignment along the 11 exons (E1-E11) of the reference <i>MLLT3</i> transcript, revealed an unexpected profile. Strikingly, the substantial <i>MLLT3</i> expression detected in HSCs was driven by a sharp ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"380-385"},"PeriodicalIF":20.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update","authors":"Feng Wang,&nbsp;Gong Chen,&nbsp;Zhen Zhang,&nbsp;Ying Yuan,&nbsp;Yi Wang,&nbsp;Yuan-Hong Gao,&nbsp;Weiqi Sheng,&nbsp;Zixian Wang,&nbsp;Xinxiang Li,&nbsp;Xianglin Yuan,&nbsp;Sanjun Cai,&nbsp;Li Ren,&nbsp;Yunpeng Liu,&nbsp;Jianmin Xu,&nbsp;Yanqiao Zhang,&nbsp;Houjie Liang,&nbsp;Xicheng Wang,&nbsp;Aiping Zhou,&nbsp;Jianming Ying,&nbsp;Guichao Li,&nbsp;Muyan Cai,&nbsp;Gang Ji,&nbsp;Taiyuan Li,&nbsp;Jingyu Wang,&nbsp;Hanguang Hu,&nbsp;Kejun Nan,&nbsp;Liuhong Wang,&nbsp;Suzhan Zhang,&nbsp;Jin Li,&nbsp;Rui-Hua Xu","doi":"10.1002/cac2.12639","DOIUrl":"10.1002/cac2.12639","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (<i>POLE</i>)/ DNA polymerase delta 1 (<i>POLD1</i>) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"332-379"},"PeriodicalIF":20.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current status and perspectives of esophageal cancer: a comprehensive review","authors":"Wei Jiang,&nbsp;Bo Zhang,&nbsp;Jiaqi Xu,&nbsp;Liyan Xue,&nbsp;Luhua Wang","doi":"10.1002/cac2.12645","DOIUrl":"10.1002/cac2.12645","url":null,"abstract":"<p>Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"281-331"},"PeriodicalIF":20.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orchestrated desaturation reprogramming from stearoyl-CoA desaturase to fatty acid desaturase 2 in cancer epithelial-mesenchymal transition and metastasis","authors":"Zhicong Chen,&nbsp;Yanqing Gong,&nbsp;Fukai Chen,&nbsp;Hyeon Jeong Lee,&nbsp;Jinqin Qian,&nbsp;Jing Zhao,&nbsp;Wenpeng Zhang,&nbsp;Yamin Li,&nbsp;Yihui Zhou,&nbsp;Qiaobing Xu,&nbsp;Yu Xia,&nbsp;Liqun Zhou,&nbsp;Ji-Xin Cheng","doi":"10.1002/cac2.12644","DOIUrl":"10.1002/cac2.12644","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adaptative desaturation in fatty acid (FA) is an emerging hallmark of cancer metabolic plasticity. Desaturases such as stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) have been implicated in multiple cancers, and their dominant and compensatory effects have recently been highlighted. However, how tumors initiate and sustain their self-sufficient FA desaturation to maintain phenotypic transition remains elusive. This study aimed to explore the molecular orchestration of SCD and FADS2 and their specific reprogramming mechanisms in response to cancer progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The potential interactions between SCD and FADS2 were explored by bioinformatics analyses across multiple cancer cohorts, which guided subsequent functional and mechanistic investigations. The expression levels of desaturases were investigated with online datasets and validated in both cancer tissues and cell lines. Specific desaturation activities were characterized through various isomer-resolved lipidomics methods and sensitivity assays using desaturase inhibitors. In-situ lipid profiling was conducted using multiplex stimulated Raman scattering imaging. Functional assays were performed both in vitro and in vivo, with RNA-sequencing employed for the mechanism verification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After integration of the RNA-protein-metabolite levels, the data revealed that a reprogramming from SCD-dependent to FADS2-dependent desaturation was linked to cancer epithelial-mesenchymal transition (EMT) and progression in both patients and cell lines. FADS2 overexpression and SCD suppression concurrently maintained EMT plasticity. A FADS2/β-catenin self-reinforcing feedback loop facilitated the degree of lipid unsaturation, membrane fluidity, metastatic potential and EMT signaling. Moreover, SCD inhibition triggered a lethal apoptosis but boosted survival plasticity by inducing EMT and enhancing FA uptake via adenosine monophosphate-activated protein kinase activation. Notably, this desaturation reprogramming increased transforming growth factor-β2, effectively sustaining aggressive phenotypes and metabolic plasticity during EMT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings revealed a metabolic reprogramming from SCD-dependent to FADS2-dependent desaturation during cancer EMT and progression, which concurrently supports EMT plasticity. Targeting desaturation reprogramming represents a potential vulnerability for cancer metabolic therapy.</p>\u0000 ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"245-280"},"PeriodicalIF":20.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein","authors":"Chenyi Shao,&nbsp;Yingyi Zhang,&nbsp;Hang Li,&nbsp;Jiajia Chen,&nbsp;Ting Huang,&nbsp;Jiaze Li,&nbsp;Simeng Wen,&nbsp;Sen Wang,&nbsp;Saijun Fan,&nbsp;Yu Zhao","doi":"10.1002/cac2.12636","DOIUrl":"10.1002/cac2.12636","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post-RT to understand the molecular mechanisms of their resistance to ICB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA-sequencing (scRNA-seq) was used to profile senescent cancer cell clusters induced by RT in LNCaP cells. The expression and phosphorylation levels of ataxia telangiectasia and Rad3-related protein (ATR) were assessed by immunohistochemistry in clinical samples from patients with or without RT. Co-immunoprecipitation, mutagenesis, and Western blotting were used to measure the interactions between proteins. Xenograft experiments were performed to assess the tumor immune response in the mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a subset of PCa cells that exhibited resistance to RT, characterized by a reduced antigen presentation capability, which enhanced their ability to evade immune detection and resist cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade. scRNA-seq revealed that the senescent state was a transient phase of PCa cells post-RT, particularly in CTLA-4 blockade treatment-resistant cells. This state was marked by increased cytosolic ATR level. Cytosolic ATR phosphorylated CD86 in its cytosolic domain and enhanced the interaction between CD86 and its E3 ligase MARCH1 through electrostatic attraction. Depletion or inhibition of Atr increased the sensitivity to immune attack and improved responses to anti-Ctla-4 antibody treatment in a mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that the activation of cytosolic ATR, which is associated with cellular senescence, impedes the effectiveness of combined RT and ICB treatments. This discovery may provide valuable insights for improving the efficacy of combined RT and ICB therapies in PCa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"218-244"},"PeriodicalIF":20.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival impact of early MRI progression after stereotactic radiotherapy for brain metastases","authors":"Moncef Morjani,&nbsp;Brieg Dissaux,&nbsp;Victor Nguyen,&nbsp;Gurvan Dissaux,&nbsp;Olivier Pradier,&nbsp;Solène Querellou,&nbsp;Romuald Seizeur,&nbsp;Ulrike Schick,&nbsp;François Lucia,&nbsp;Vincent Bourbonne","doi":"10.1002/cac2.12641","DOIUrl":"10.1002/cac2.12641","url":null,"abstract":"&lt;p&gt;The management of brain metastases (BMs) has rapidly evolved in recent years [&lt;span&gt;1&lt;/span&gt;]. It is estimated that 20%-40% of cancer patients will develop BMs during their disease, while prevalence will probably grow thanks to the increased efficacy of systemic treatments. Whole-brain radiotherapy has long been the first-line treatment for BMs. Large-scale international clinical trials conducted over the past decade have established that stereotactic radiotherapy (SRT) is the treatment of choice for the management of patients harboring up to 3-5 metastases with the compromise of increased distant brain failure (DBF) rates [&lt;span&gt;2&lt;/span&gt;]. Selection of patients and appropriate monitoring of patients remain a challenge.&lt;/p&gt;&lt;p&gt;Post-SRT monitoring is crucial to identify DBF and possibly lead to substantial treatment modifications. Indeed, several studies have shown that patients with symptomatic cerebral recurrences have poorer survival rates and generate higher costs for the healthcare system than asymptomatic patients whose recurrences have been detected by routine surveillance imaging [&lt;span&gt;3&lt;/span&gt;]. A consensus seems to be emerging on the need for magnetic resonance imaging (MRI) every 3 months after brain SRT [&lt;span&gt;4-6&lt;/span&gt;]. In our institution, the first MRI evaluation (MRI&lt;sub&gt;1&lt;/sub&gt;) is performed around 6 weeks after SRT. To our knowledge, no study has evaluated the benefit of early MRI evaluation (before 2 months) nor the survival impact of the MRI delay after SRT. We hypothesize that early MRI can lead to anticipated treatment changes and thus may impact survival. The full methodology is available in Supplementary Materials.&lt;/p&gt;&lt;p&gt;Between January 2014 and July 2022, 678 adult patients with solid cancer were treated with SRT at the Brest University Hospital, corresponding overall to 869 treatment courses and 1,681 lesions. Among these patients, 143 SRT courses did not have an available post-SRT MRI (MRI&lt;sub&gt;1&lt;/sub&gt;) and 41 courses had a histology that did not allow calculation of the Disease Specific-Graded Prognostic Assessment (DS-GPA) score. Of the remaining 685 treatment courses, 80 treatment courses were not considered because MRI&lt;sub&gt;1&lt;/sub&gt; was performed before 30 days (&lt;i&gt;n&lt;/i&gt; = 17) or after 90 days (&lt;i&gt;n&lt;/i&gt; = 63). The final cohort thus consisted of 488 patients, 605 treatment courses and 1,172 treated BMs (mean number of 1.93 BMs per SRT course). A flowchart is available (Supplementary Figure S1). The mean age at the time of SRT was 63.2 years (inter-quartile range [IQR] = 57.3-70.4), and the most common histology was lung (69.9%), particularly pulmonary adenocarcinoma (91.3%). Most patients were male (53.5%), with a maintained performance status: Karnofsky score of 90% (IQR = 80-90) despite a relatively high percentage of symptomatic BMs (44.1%). The clinical status at the time of treatment was most often oligo-progression (61.7%). At the time of SRT, the DS-GPA-score was between 2 and 3 for 44.0% and above or equal to","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 3","pages":"215-217"},"PeriodicalIF":20.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}