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Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers. 在早发性癌症日益增多的时代，加速发现癌症病因以预防癌症。
IF 42.5 1区 生物学
Cell Pub Date : 2026-04-16 Epub Date: 2026-04-07 DOI: 10.1016/j.cell.2026.03.019
Mengyao Shi, Gary J Patti, Marc J Gunter, Ramaswamy Govindan, Iris Lansdorp-Vogelaar, Ting Wang, Jeffrey P Townsend, Graham A Colditz, Yasmine Belkaid, Yin Cao
{"title":"Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers.","authors":"Mengyao Shi, Gary J Patti, Marc J Gunter, Ramaswamy Govindan, Iris Lansdorp-Vogelaar, Ting Wang, Jeffrey P Townsend, Graham A Colditz, Yasmine Belkaid, Yin Cao","doi":"10.1016/j.cell.2026.03.019","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.019","url":null,"abstract":"<p><p>Cancer in younger adults is rising globally, with notable birth-cohort effects. This epidemiological shift underscores the urgent need to accelerate the identification of novel causes and underlying biological networks, with the aim of translating these insights into prevention and interception strategies. In this perspective, we revisit the major milestones in the discovery of cancer causes and outline challenges that hinder progress. To address these challenges, we advocate closer integration of epidemiologic and mechanistic studies and propose three interconnected frameworks that extend current epidemiologic approaches: a tissue ecosystem-anchored framework for cancer cause discovery, a biological state-based framework for precision cancer risk assessment, and a dynamic framework to characterize cancer preventability. This roadmap aims to stimulate conceptual, resource, and methodological advances to accelerate cancer etiology research and prevention in the era of rising early-onset cancers.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"189 8","pages":"2232-2253"},"PeriodicalIF":42.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hallmarks of setting up a successful patient advocacy group 这是建立一个成功的病人权益组织的标志
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.028
Andrea Anampa-Guzmán, Patrick McGuire, Fiorella S. Gagliardi, Yi Lin Teh, Karen Nakala, Dozie Akwarandu
{"title":"Hallmarks of setting up a successful patient advocacy group","authors":"Andrea Anampa-Guzmán, Patrick McGuire, Fiorella S. Gagliardi, Yi Lin Teh, Karen Nakala, Dozie Akwarandu","doi":"10.1016/j.cell.2026.03.028","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.028","url":null,"abstract":"Patient advocacy has the potential to contribute to effective cancer care with real-world impact, regardless of a country’s socioeconomic status. Here, we asked representatives of patient advocacy groups for key considerations to overcome challenges when starting out in resource-limited settings. We are grateful to them for sharing their voices and for their relentless fight toward making cancer care more accessible.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"3 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Hallmarks of Cancer: 25 years guiding discovery and therapy 癌症的标志：25年指导发现和治疗
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.033
{"title":"The Hallmarks of Cancer: 25 years guiding discovery and therapy","authors":"","doi":"10.1016/j.cell.2026.03.033","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.033","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Few diseases have challenged scientists and clinicians as persistently as cancer. Tumors arise from our own cells, yet they evolve into complex and adaptive systems capable of resisting therapy and reshaping both the tissues and the organism that hosts them. The resulting diversity and dynamism have long complicated our ability to conceptualize cancer, let alone treat it. In 2000, Robert Weinberg and Douglas Hanahan offered a unifying perspective with the proposal of the six Hallmarks of</section></section>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"66 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tackling the complexity of cancer with generative models. 用生成模型解决癌症的复杂性。
IF 42.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.027
Ashley Mae Conard, Madeline Hughes, James Hall, Neil Tenenholtz, Eric Zimmermann, Lorin Crawford, Ava P Amini, Kristen Severson
{"title":"Tackling the complexity of cancer with generative models.","authors":"Ashley Mae Conard, Madeline Hughes, James Hall, Neil Tenenholtz, Eric Zimmermann, Lorin Crawford, Ava P Amini, Kristen Severson","doi":"10.1016/j.cell.2026.03.027","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.027","url":null,"abstract":"<p><p>The Hallmarks of Cancer framework has played a seminal role in developing our understanding of cancer biology. By design, these hallmarks abstract cancer into a common set of functional capabilities. The hallmarks thus constitute an intentionally reductionist framework that has unified diverse observations and yielded valuable mechanistic insight, while leaving unresolved how these processes interact across scales. Complementary tools are therefore needed to capture cancer's inherently complex, multimodal, and multiscale nature. Here, we posit that generative models, built on the recent advances of artificial intelligence, are the key technology to capture this complexity and to thereby improve how we diagnose, understand, and intervene in cancer. Specifically, because of their ability to recognize complex patterns, process unstructured inputs, and synthesize multimodal inputs, generative models are poised to usher in a new era of biological discovery and clinical care. Ultimately, we envision a synergistic cycle wherein generative models of cancer and the Hallmarks of Cancer complement one another, the former driving hypothesis generation and discovery and the latter guiding the prioritization and development of new measurement tools.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":"189 8","pages":"2218-2231"},"PeriodicalIF":42.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell death in cancer 癌症中的细胞死亡
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.024
Marcus Conrad, Andreas Strasser, Philipp J. Jost, Junying Yuan, Feng Shao, Peter Vandenabeele, Adam Wahida
{"title":"Cell death in cancer","authors":"Marcus Conrad, Andreas Strasser, Philipp J. Jost, Junying Yuan, Feng Shao, Peter Vandenabeele, Adam Wahida","doi":"10.1016/j.cell.2026.03.024","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.024","url":null,"abstract":"“Evasion of cell death” is a hallmark of cancer, enabling transformed cells to withstand oncogenic and therapeutic stress. Restoring cancer cell death is an appealing strategy but requires a deep understanding of cell death programs. Over the past two decades, the cell death field has expanded from apoptosis to include necroptosis, pyroptosis, ferroptosis, and other emerging programs, reshaping cancer biology and revealing therapeutic opportunities. While apoptosis remains the primary radiation- and chemotherapy-induced cell death program, non-apoptotic programs can drive inflammatory responses and orchestrate the interplay among tumor, stroma, and immune components, influencing immunotherapy outcomes. Ferroptosis, an iron-dependent, lipid peroxidation-driven cell death modality, lacks a canonical induction signal and arises from perturbations in lipid, iron, and redox metabolism. This review presents a unified framework for understanding the roles of major cell death programs in cancer development, progression, and treatment response, as well as addressing resistance to cancer cell death and immune suppression.“Our bodies are made of cells that live, and just as surely, of cells that must die.” –S. Brenner","PeriodicalId":9656,"journal":{"name":"Cell","volume":"46 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping intratumor heterogeneity across layers for advancing immunotherapy 跨层绘制肿瘤内异质性以推进免疫治疗
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.025
Jean-Christophe Marine, Osnat Bartok, Shira Sagie, Pietro Paolo Vitiello, Alberto Bardelli, Chen Weller, Tian-Gen Chang, Claudia Tonelli, Stefani Spranger, Eytan Ruppin, Yardena Samuels
{"title":"Mapping intratumor heterogeneity across layers for advancing immunotherapy","authors":"Jean-Christophe Marine, Osnat Bartok, Shira Sagie, Pietro Paolo Vitiello, Alberto Bardelli, Chen Weller, Tian-Gen Chang, Claudia Tonelli, Stefani Spranger, Eytan Ruppin, Yardena Samuels","doi":"10.1016/j.cell.2026.03.025","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.025","url":null,"abstract":"Intratumor heterogeneity (ITH) encompasses genetic, epigenetic, transcriptional, proteomic, and immunopeptidomic diversity. Beyond genetic heterogeneity, it is increasingly clear that non-mutational heterogeneity and plasticity generate dynamic cancer cell states with distinct immune visibility. These layers of complexity converge on the immunopeptidome, the repertoire of peptides displayed by major histocompatibility complex molecules through which tumor cells are surveyed by T cells. Variation in antigen processing, presentation, and peptide abundance across cancer clones and cell states yields spatially and temporally distinct immunological niches that shape immune recognition and therapeutic response. Here, we summarize how multidimensional ITH manifests across cancer types and constrains immunotherapy efficacy. We propose that integrating measurements across layers is a promising direction for improving biomarker identification and informing more precise immune-based treatment strategies.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"28 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer ecosystems: A dynamic interplay across scales 癌症生态系统：跨尺度的动态相互作用
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.003
Daniela F. Quail, Johanna A. Joyce
{"title":"Cancer ecosystems: A dynamic interplay across scales","authors":"Daniela F. Quail, Johanna A. Joyce","doi":"10.1016/j.cell.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.003","url":null,"abstract":"Tumors evolve within complex, adaptive ecosystems that operate across spatial, temporal, and systemic scales. Within each tumor microenvironment, numerous diverse cell populations assemble into specialized niches that are continually shaped by systemic physiology, environmental inputs, and therapeutic pressure. Beyond the local microenvironment, cancer progression is governed by the host macroenvironment, where intrinsic biological determinants intersect with modifiable factors to collectively impact physiological fitness and tissue resilience. Here, we propose a multi-scale framework that unites tumor biology with organismal physiology and reframes therapy from eliminating malignant cells in isolation to reprogramming the cellular, vascular, and systemic networks that sustain disease. We highlight emerging approaches that aim to restore physiological equilibrium, spanning from spatial multi-omics and AI-driven pathology to immune-vascular normalization and physiological conditioning. Together, these dimensions define an integrative vision for precision oncology that bridges discovery and intervention to achieve durable and ultimately curative cancer therapy.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"29 1","pages":"2441-2463"},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting genomic instability in cancer 靶向癌症基因组不稳定性
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.035
Timothy A. Yap, H. Charles Manning, Puja Sapra, Gordon B. Mills, Mark J. O’Connor
{"title":"Targeting genomic instability in cancer","authors":"Timothy A. Yap, H. Charles Manning, Puja Sapra, Gordon B. Mills, Mark J. O’Connor","doi":"10.1016/j.cell.2026.03.035","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.035","url":null,"abstract":"Genomic instability is a defining feature of cancer, which arises when the cellular systems that maintain DNA integrity falter, enabling the accumulation of genetic and epigenetic alterations that drive malignant transformation. It is both the architect of cancer’s evolution and its Achilles’ heel. Targeting genomic instability has reshaped oncology: first through systemic chemotherapy and external beam radiation and then with poly(ADP-ribose) polymerase (PARP) inhibitors in homologous recombination repair-deficient tumors and other DNA damage response targets. Recently, tumor-targeted DNA-damaging platforms, namely antibody-drug conjugates (ADCs) and radiopharmaceuticals, have emerged alongside modern precision medicine strategies to optimize patient selection, develop rational combinations, and widen the therapeutic index.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"27 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Shared leadership, shared responsibility 共同领导，共同承担责任
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.030
Zoë S. Walters, Timothy J. Underwood
{"title":"Shared leadership, shared responsibility","authors":"Zoë S. Walters, Timothy J. Underwood","doi":"10.1016/j.cell.2026.03.030","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.030","url":null,"abstract":"In choosing to merge two independent teams, we stepped into an unconventional model of co-leadership that reshaped our scientific lives. A clinician and a scientist leading together challenged academic norms, dissolved the loneliness of traditional principal investigator roles, and created a shared patient-centered vision for translational research. By embedding patients, carers, and high-performance coaching at our core, we built a culture defined not by individual burden but by collective responsibility, sustainability, and genuine collaboration. This is our story.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"17 1","pages":""},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A recipe for chaos: Extrachromosomal DNA and the hallmarks of cancer 混乱的配方：染色体外DNA和癌症的特征
IF 64.5 1区 生物学
Cell Pub Date : 2026-04-16 DOI: 10.1016/j.cell.2026.03.011
Ivy Tsz-Lo Wong, Chris Bailey, Sihan Wu, Anton G. Henssen, Benjamin F. Cravatt, Zhijian J. Chen, Vineet Bafna, Mariam Jamal-Hanjani, Charlie Swanton, Howard Y. Chang, Paul S. Mischel
{"title":"A recipe for chaos: Extrachromosomal DNA and the hallmarks of cancer","authors":"Ivy Tsz-Lo Wong, Chris Bailey, Sihan Wu, Anton G. Henssen, Benjamin F. Cravatt, Zhijian J. Chen, Vineet Bafna, Mariam Jamal-Hanjani, Charlie Swanton, Howard Y. Chang, Paul S. Mischel","doi":"10.1016/j.cell.2026.03.011","DOIUrl":"https://doi.org/10.1016/j.cell.2026.03.011","url":null,"abstract":"Some aggressive cancers exhibit a level of rapid genome change and therapy resistance that is difficult to explain. Research over the past decade has shown that extrachromosomal DNA (ecDNA) can be the cause. When oncogenic genetic elements untether from chromosomes and no longer follow Mendelian inheritance, genomic chaos and accelerated evolution ensue, generating unique ecDNA biology and non-traditional therapeutic vulnerabilities distinct from traditional mutation-targeting approaches. Here, we put forward a holistic view where ecDNA is integrated into the broader Hallmarks of Cancer framework to better understand the problem and chart a path forward.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"47 1","pages":"2307-2321"},"PeriodicalIF":64.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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