Pub Date : 2024-10-17DOI: 10.1016/j.ccell.2024.09.014
William L. Hwang, Ella N. Perrault, Alexander Birbrair, Brandi J. Mattson, David H. Gutmann, Donald J. Mabbott, Edna Cukierman, Elizabeth A. Repasky, Erica K. Sloan, Hui Zong, Ihsan Ekin Demir, Jami L. Saloman, Jeremy C. Borniger, Jian Hu, Jorg Dietrich, Joshua J. Breunig, Kaan Çifcibaşı, Khalil Ali Ahmad Kasm, Manuel Valiente, Max Wintermark, Moran Amit
Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.
{"title":"Integrating priorities at the intersection of cancer and neuroscience","authors":"William L. Hwang, Ella N. Perrault, Alexander Birbrair, Brandi J. Mattson, David H. Gutmann, Donald J. Mabbott, Edna Cukierman, Elizabeth A. Repasky, Erica K. Sloan, Hui Zong, Ihsan Ekin Demir, Jami L. Saloman, Jeremy C. Borniger, Jian Hu, Jorg Dietrich, Joshua J. Breunig, Kaan Çifcibaşı, Khalil Ali Ahmad Kasm, Manuel Valiente, Max Wintermark, Moran Amit","doi":"10.1016/j.ccell.2024.09.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.014","url":null,"abstract":"Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"2 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.ccell.2024.09.011
Evelyn Fitzsimons, Danwen Qian, Andrei Enica, Krupa Thakkar, Marcellus Augustine, Samuel Gamble, James L. Reading, Kevin Litchfield
Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment. We explore associations between B cell subsets and checkpoint inhibitor therapy responses, finding subset-specific effects on overall response. Additionally, we examine B and T cell crosstalk, identifying unique ligand-receptor pairs for specific B cell subsets, spatially validated. This comprehensive dataset serves as a valuable resource, providing a detailed atlas that enhances the understanding of B cell complexity in tumors and opens new avenues for research and therapeutic strategies.
肿瘤浸润 B 细胞在肿瘤发生、发展和预后中起着重要作用，但目前还缺乏一个全面的分类系统。为了填补这一空白，我们在一个大型样本群中绘制了肿瘤浸润B细胞和浆细胞的泛癌症单细胞RNA测序（scRNA-seq）图谱。我们确定了关键的 B 细胞亚群特征，揭示了不同的亚群，并强调了这些细胞在肿瘤微环境中的异质性和功能多样性。我们探讨了 B 细胞亚群与检查点抑制剂治疗反应之间的关联，发现了亚群对总体反应的特异性影响。此外，我们还研究了 B 细胞和 T 细胞的串扰，为特定的 B 细胞亚群确定了独特的配体-受体对，并进行了空间验证。这个全面的数据集是一个宝贵的资源，它提供了一个详细的图谱，加深了人们对肿瘤中 B 细胞复杂性的了解，并为研究和治疗策略开辟了新的途径。
{"title":"A pan-cancer single-cell RNA-seq atlas of intratumoral B cells","authors":"Evelyn Fitzsimons, Danwen Qian, Andrei Enica, Krupa Thakkar, Marcellus Augustine, Samuel Gamble, James L. Reading, Kevin Litchfield","doi":"10.1016/j.ccell.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.011","url":null,"abstract":"Tumor-infiltrating B cells play a significant role in tumor development, progression, and prognosis, yet a comprehensive classification system is lacking. To address this gap, we present a pan-cancer single-cell RNA sequencing (scRNA-seq) atlas of tumor-infiltrating B and plasma cells across a large sample cohort. We identify key B cell subset signatures, revealing distinct subpopulations and highlighting the heterogeneity and functional diversity of these cells in the tumor microenvironment. We explore associations between B cell subsets and checkpoint inhibitor therapy responses, finding subset-specific effects on overall response. Additionally, we examine B and T cell crosstalk, identifying unique ligand-receptor pairs for specific B cell subsets, spatially validated. This comprehensive dataset serves as a valuable resource, providing a detailed atlas that enhances the understanding of B cell complexity in tumors and opens new avenues for research and therapeutic strategies.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"229 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2+ NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by in vitro organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.
{"title":"A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial","authors":"Xiaobin Shang, Yongjie Xie, Jinpu Yu, Chen Zhang, Gang Zhao, Fei Liang, Liang Liu, Weihong Zhang, Runmei Li, Wenwen Yu, Jie Yue, Chuangui Chen, Xiaofeng Duan, Zhao Ma, Zuoyu Chen, Yanjuan Xiong, Fan Yang, Jianyu Xiao, Rui Zhang, Pengpeng Liu, Hongjing Jiang","doi":"10.1016/j.ccell.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.008","url":null,"abstract":"In this phase II study, 47 patients with locally advanced, resectable esophageal squamous cell carcinoma (ESCC) received three cycles of pembrolizumab plus chemotherapy, followed by Da Vinci robot-assisted surgery. The primary endpoints were safety and major pathological response (MPR). Key secondary endpoints included complete pathological response (pCR) and survival. No grade ≥3 adverse events or surgical delays occurred during neoadjuvant therapy. Among 46 patients studied for efficacy, the MPR and pCR rates were 72% and 41%, respectively. After a median follow-up of 27.2 months, the 2-year overall survival (OS) and disease-free survival (DFS) rates were 91% and 89%, respectively. Expansion of TRGC2<sup>+</sup> NKT cells in peripheral blood correlated with neoadjuvant treatment effectiveness, which was validated by <em>in vitro</em> organoid experiments and external cancer datasets, and its functional classification and mechanism of action were further explored. These findings show preoperative pembrolizumab plus chemotherapy is a promising therapeutic strategy for resectable ESCC.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"29 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.ccell.2024.09.013
Colleen Sturdevant, Yuliya Pylayeva-Gupta
The role of B cells in cancer remains incompletely understood. Three recent publications, including a study by Fitzsimons et al. in this issue of Cancer Cell,1 use single-cell RNA sequencing to define pan-cancer atlases of tumor-infiltrating B cell subsets, paving the way for profound advances in our understanding of B cell-dependent antitumor immunity.
人们对 B 细胞在癌症中的作用仍然知之甚少。最近发表的三篇论文，包括 Fitzsimons 等人在本期《癌细胞》（Cancer Cell）1 上发表的一项研究，利用单细胞 RNA 测序确定了肿瘤浸润 B 细胞亚群的泛癌症图谱，为我们深入了解 B 细胞依赖性抗肿瘤免疫铺平了道路。
{"title":"B cell heterogeneity in cancer comes of age","authors":"Colleen Sturdevant, Yuliya Pylayeva-Gupta","doi":"10.1016/j.ccell.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.013","url":null,"abstract":"The role of B cells in cancer remains incompletely understood. Three recent publications, including a study by Fitzsimons et al. in this issue of <em>Cancer Cell</em>,<span><span><sup>1</sup></span></span> use single-cell RNA sequencing to define pan-cancer atlases of tumor-infiltrating B cell subsets, paving the way for profound advances in our understanding of B cell-dependent antitumor immunity.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"9 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ccell.2024.09.010
Claudia Galassi, Timothy A. Chan, Ilio Vitale, Lorenzo Galluzzi
According to the widely accepted “three Es” model, the host immune system eliminates malignant cell precursors and contains microscopic neoplasms in a dynamic equilibrium, preventing cancer outgrowth until neoplastic cells acquire genetic or epigenetic alterations that enable immune escape. This immunoevasive phenotype originates from various mechanisms that can be classified under a novel “three Cs” conceptual framework: (1) camouflage, which hides cancer cells from immune recognition, (2) coercion, which directly or indirectly interferes with immune effector cells, and (3) cytoprotection, which shields malignant cells from immune cytotoxicity. Blocking the ability of neoplastic cells to evade the host immune system is crucial for increasing the efficacy of modern immunotherapy and conventional therapeutic strategies that ultimately activate anticancer immunosurveillance. Here, we review key hallmarks of cancer immune evasion under the “three Cs” framework and discuss promising strategies targeting such immunoevasive mechanisms.
{"title":"The hallmarks of cancer immune evasion","authors":"Claudia Galassi, Timothy A. Chan, Ilio Vitale, Lorenzo Galluzzi","doi":"10.1016/j.ccell.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.010","url":null,"abstract":"According to the widely accepted “three Es” model, the host immune system <u>e</u>liminates malignant cell precursors and contains microscopic neoplasms in a dynamic <u>e</u>quilibrium, preventing cancer outgrowth until neoplastic cells acquire genetic or epigenetic alterations that enable immune <u>e</u>scape. This immunoevasive phenotype originates from various mechanisms that can be classified under a novel “three Cs” conceptual framework: (1) <u>c</u>amouflage, which hides cancer cells from immune recognition, (2) <u>c</u>oercion, which directly or indirectly interferes with immune effector cells, and (3) <u>c</u>ytoprotection, which shields malignant cells from immune cytotoxicity. Blocking the ability of neoplastic cells to evade the host immune system is crucial for increasing the efficacy of modern immunotherapy and conventional therapeutic strategies that ultimately activate anticancer immunosurveillance. Here, we review key hallmarks of cancer immune evasion under the “three Cs” framework and discuss promising strategies targeting such immunoevasive mechanisms.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"62 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ccell.2024.09.009
Rei Kudo, Anton Safonov, Catherine Jones, Enrico Moiso, Jonathan R. Dry, Hong Shao, Sharanya Nag, Edaise M. da Silva, Selma Yeni Yildirim, Qing Li, Elizabeth O'Connell, Payal Patel, Marie Will, Atsushi Fushimi, Marimar Benitez, Martina Bradic, Li Fan, Harikrishna Nakshatri, Dhivya R. Sudhan, Christopher R. Denz, Sarat Chandarlapaty
Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence of phospho-p130 prevents DREAM complex assembly, enabling cell-cycle re-entry and tumor progression. Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.
{"title":"Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion","authors":"Rei Kudo, Anton Safonov, Catherine Jones, Enrico Moiso, Jonathan R. Dry, Hong Shao, Sharanya Nag, Edaise M. da Silva, Selma Yeni Yildirim, Qing Li, Elizabeth O'Connell, Payal Patel, Marie Will, Atsushi Fushimi, Marimar Benitez, Martina Bradic, Li Fan, Harikrishna Nakshatri, Dhivya R. Sudhan, Christopher R. Denz, Sarat Chandarlapaty","doi":"10.1016/j.ccell.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.009","url":null,"abstract":"Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority of patients experience long-term disease control. Using a large, clinically annotated cohort of patients with metastatic hormone receptor-positive (HR+) breast cancer, we identify <em>TP53</em> loss (27.6%) and <em>MDM2</em> amplification (6.4%) to be associated with lack of long-term disease control. Human breast cancer models reveal that p53 loss does not alter CDK4/6 activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence of phospho-p130 prevents DREAM complex assembly, enabling cell-cycle re-entry and tumor progression. Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"8 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ccell.2024.09.005
Xiangyun Mao, G. Caleb Alexander, Guanqiao Li
We compare the clinical trial success rates of products receiving US Food and Drug Administration (FDA) accelerated approval (AA) to those approved without using this pathway. Our findings raise important questions about how the AA pathway can best optimize early access to therapeutics that are ultimately proven safe and effective.
我们比较了获得美国食品和药物管理局（FDA）加速批准（AA）的产品与未使用该途径获得批准的产品的临床试验成功率。我们的研究结果提出了一些重要的问题，即 AA 途径如何才能最好地优化治疗药物的早期使用，并最终证明其安全有效。
{"title":"Accelerated approvals: Early-phase success or premature authorization?","authors":"Xiangyun Mao, G. Caleb Alexander, Guanqiao Li","doi":"10.1016/j.ccell.2024.09.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.005","url":null,"abstract":"We compare the clinical trial success rates of products receiving US Food and Drug Administration (FDA) accelerated approval (AA) to those approved without using this pathway. Our findings raise important questions about how the AA pathway can best optimize early access to therapeutics that are ultimately proven safe and effective.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"227 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ccell.2024.09.007
Ian P. MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T. Ruffin, Sarah Taylor, T. Rinda Soong, Riyue Bao, Lan G. Coffman, Tullia C. Bruno
Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.
{"title":"The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions","authors":"Ian P. MacFawn, Grant Magnon, Grace Gorecki, Sheryl Kunning, Rufiaat Rashid, Medard Ernest Kaiza, Huda Atiya, Ayana T. Ruffin, Sarah Taylor, T. Rinda Soong, Riyue Bao, Lan G. Coffman, Tullia C. Bruno","doi":"10.1016/j.ccell.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.007","url":null,"abstract":"Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"62 25 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.ccell.2024.09.006
Hongde Li, Linchong Sun, Ping Gao, Hai Hu
Lactylation, a recently identified post-translational modification, has initially been linked to gene transcription regulation through epigenetic mechanisms. However, its role in tumorigenesis—whether as a major driver or a minor regulator—remains uncertain. Here, we summarize the current understanding of lactylation and discuss the inherent challenges in definitively attributing specific biological roles to this modification. We emphasize the necessity for precise methodologies to manipulate lactylation levels within pathophysiologically relevant conditions. Further investigation is required to determine whether lactylation plays a critical role in tumor biology or merely reflects secondary metabolic alterations.
{"title":"Lactylation in cancer: Current understanding and challenges","authors":"Hongde Li, Linchong Sun, Ping Gao, Hai Hu","doi":"10.1016/j.ccell.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.006","url":null,"abstract":"Lactylation, a recently identified post-translational modification, has initially been linked to gene transcription regulation through epigenetic mechanisms. However, its role in tumorigenesis—whether as a major driver or a minor regulator—remains uncertain. Here, we summarize the current understanding of lactylation and discuss the inherent challenges in definitively attributing specific biological roles to this modification. We emphasize the necessity for precise methodologies to manipulate lactylation levels within pathophysiologically relevant conditions. Further investigation is required to determine whether lactylation plays a critical role in tumor biology or merely reflects secondary metabolic alterations.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"76 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1016/j.ccell.2024.09.004
Nikolas Andreas Stevens, Nina Drewa, Varun Venkataramani
Gliomas exhibit significant molecular diversity and poor prognosis. In this issue of Cancer Cell, Curry et al. apply Patch-seq on human glioma samples uncovering hybrid cells with glial and neuronal features, capable of firing action potentials in isocitrate dehydrogenase mutant gliomas. These findings highlight the importance of neural features in tumor biology and progression.
{"title":"Spark in the darkness: Discovering action potentials in brain tumors","authors":"Nikolas Andreas Stevens, Nina Drewa, Varun Venkataramani","doi":"10.1016/j.ccell.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.09.004","url":null,"abstract":"Gliomas exhibit significant molecular diversity and poor prognosis. In this issue of <em>Cancer Cell</em>, Curry et al. apply Patch-seq on human glioma samples uncovering hybrid cells with glial and neuronal features, capable of firing action potentials in isocitrate dehydrogenase mutant gliomas. These findings highlight the importance of neural features in tumor biology and progression.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"5 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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