Pub Date : 2025-10-01DOI: 10.1038/s43018-025-01044-8
Melanie Senior
Investment continues as the field awaits phase 3 readouts for next-generation radioligand therapies in 2026.
投资仍在继续，该领域将在2026年等待下一代放射配体疗法的3期读数。
{"title":"Radiopharma pipeline builds ahead of key data","authors":"Melanie Senior","doi":"10.1038/s43018-025-01044-8","DOIUrl":"10.1038/s43018-025-01044-8","url":null,"abstract":"Investment continues as the field awaits phase 3 readouts for next-generation radioligand therapies in 2026.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 12","pages":"1905-1908"},"PeriodicalIF":28.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206918","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 : 2025-09-25DOI: 10.1038/s43018-025-01047-5
Kaloyan M. Tsanov, Francisco M. Barriga, Yu-Jui Ho, Direna Alonso-Curbelo, Geulah Livshits, Sha Tian, Richard P. Koche, Timour Baslan, Janelle Simon, Alexandra N. Wuest, José Reyes, Jin Park, Wei Luan, John E. Wilkinson, Umesh Bhanot, Jordana Ray-Kirton, Ignas Masilionis, Nevenka Dimitrova, Christine A. Iacobuzio-Donahue, Ronan Chaligné, Dana Pe’er, Joan Massagué, Scott W. Lowe
The role of driver gene mutations in sustaining tumor growth at metastatic sites is poorly understood. SMAD4 inactivation is a paradigm of such mutations and a hallmark of pancreatic ductal adenocarcinoma (PDAC). To determine whether metastatic tumors are dependent on SMAD4 inactivation, we developed a mouse model of PDAC that enables spatiotemporal control of Smad4 expression. While Smad4 inactivation in the premalignant pancreas facilitated the formation of primary tumors, Smad4 reactivation in metastatic disease suppressed liver metastases but promoted lung metastases. These divergent effects were underpinned by organ-biased differences in the tumor cells’ chromatin state that emerged in the premalignant pancreas and were distinguished by the dominance of KLF4 versus RUNX1 transcription factors. Our results show how epigenetic states favored by the organ of residence can influence the output of driver mutations in metastatic tumors, which has implications for interpreting tumor genetics and therapeutically targeting metastatic disease. Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.
{"title":"SMAD4 induces opposite effects on metastatic growth from pancreatic tumors depending on the organ of residence","authors":"Kaloyan M. Tsanov, Francisco M. Barriga, Yu-Jui Ho, Direna Alonso-Curbelo, Geulah Livshits, Sha Tian, Richard P. Koche, Timour Baslan, Janelle Simon, Alexandra N. Wuest, José Reyes, Jin Park, Wei Luan, John E. Wilkinson, Umesh Bhanot, Jordana Ray-Kirton, Ignas Masilionis, Nevenka Dimitrova, Christine A. Iacobuzio-Donahue, Ronan Chaligné, Dana Pe’er, Joan Massagué, Scott W. Lowe","doi":"10.1038/s43018-025-01047-5","DOIUrl":"10.1038/s43018-025-01047-5","url":null,"abstract":"The role of driver gene mutations in sustaining tumor growth at metastatic sites is poorly understood. SMAD4 inactivation is a paradigm of such mutations and a hallmark of pancreatic ductal adenocarcinoma (PDAC). To determine whether metastatic tumors are dependent on SMAD4 inactivation, we developed a mouse model of PDAC that enables spatiotemporal control of Smad4 expression. While Smad4 inactivation in the premalignant pancreas facilitated the formation of primary tumors, Smad4 reactivation in metastatic disease suppressed liver metastases but promoted lung metastases. These divergent effects were underpinned by organ-biased differences in the tumor cells’ chromatin state that emerged in the premalignant pancreas and were distinguished by the dominance of KLF4 versus RUNX1 transcription factors. Our results show how epigenetic states favored by the organ of residence can influence the output of driver mutations in metastatic tumors, which has implications for interpreting tumor genetics and therapeutically targeting metastatic disease. Using mouse pancreatic cancer models, Tsanov et al. show that reactivation of SMAD4 at metastatic sites promotes tumor growth in the lung through RUNX1 but restrains metastatic growth through KLF4 in the liver, influenced by organ-specific epigenetic states.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 11","pages":"1839-1856"},"PeriodicalIF":28.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-025-01047-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149984","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}
Pub Date : 2025-09-19DOI: 10.1038/s43018-025-01045-7
Kar Wei Chin, Wan-Qin Chong, Boon Cher Goh, Brigette B. Y. Ma
Propelled by a growing understanding of nasopharyngeal carcinoma pathogenesis through elucidation of its genomic and immune landscape, therapy has progressed from radiotherapy alone to combined chemotherapy and immunotherapy. This Clinical Outlook focuses on recent milestones and future directions for patients with nasopharyngeal carcinoma.
{"title":"Evolving landscape of nasopharyngeal carcinoma therapy","authors":"Kar Wei Chin, Wan-Qin Chong, Boon Cher Goh, Brigette B. Y. Ma","doi":"10.1038/s43018-025-01045-7","DOIUrl":"10.1038/s43018-025-01045-7","url":null,"abstract":"Propelled by a growing understanding of nasopharyngeal carcinoma pathogenesis through elucidation of its genomic and immune landscape, therapy has progressed from radiotherapy alone to combined chemotherapy and immunotherapy. This Clinical Outlook focuses on recent milestones and future directions for patients with nasopharyngeal carcinoma.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1480-1482"},"PeriodicalIF":28.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092153","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 : 2025-09-12DOI: 10.1038/s43018-025-01046-6
Vincenzo Giacco
The ESMO Targeted Anticancer Therapies Asia Congress took place in Hong Kong from 18–20 July 2025. Focusing on innovation, early clinical trials, and regulatory insights, the meeting advanced key discussions shaping the future of cancer research and treatment in the region.
{"title":"Key highlights from the ESMO Targeted Anticancer Therapies Asia Congress 2025","authors":"Vincenzo Giacco","doi":"10.1038/s43018-025-01046-6","DOIUrl":"10.1038/s43018-025-01046-6","url":null,"abstract":"The ESMO Targeted Anticancer Therapies Asia Congress took place in Hong Kong from 18–20 July 2025. Focusing on innovation, early clinical trials, and regulatory insights, the meeting advanced key discussions shaping the future of cancer research and treatment in the region.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1488-1489"},"PeriodicalIF":28.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054586","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 : 2025-09-11DOI: 10.1038/s43018-025-01042-w
S. Cazzamalli, E. Puca, D. Neri
Drug conjugates have emerged as promising tumor-targeted cytotoxics with an improved therapeutic index compared to classical chemotherapeutics. Although traditionally based on antibody ligands, high-throughput screening methods, such as peptide display and DNA-encoded chemical libraries, have enabled the isolation of ultra-high-affinity small ligands and the generation of drug conjugates with better tumor-targeting performance. This Perspective examines the history, major clinical milestones and future of drug conjugates for cancer treatment. We also discuss a new wave of combination modalities, linker strategies, and the development of conjugates based on large and small delivery vehicles. Neri and colleagues discuss the development of drug conjugates for cancer therapy, focusing on current and future opportunities to improve tumor-targeting efficacy with small molecule–drug conjugates and combination therapies.
{"title":"Past, present and future of drug conjugates for cancer therapy","authors":"S. Cazzamalli, E. Puca, D. Neri","doi":"10.1038/s43018-025-01042-w","DOIUrl":"10.1038/s43018-025-01042-w","url":null,"abstract":"Drug conjugates have emerged as promising tumor-targeted cytotoxics with an improved therapeutic index compared to classical chemotherapeutics. Although traditionally based on antibody ligands, high-throughput screening methods, such as peptide display and DNA-encoded chemical libraries, have enabled the isolation of ultra-high-affinity small ligands and the generation of drug conjugates with better tumor-targeting performance. This Perspective examines the history, major clinical milestones and future of drug conjugates for cancer treatment. We also discuss a new wave of combination modalities, linker strategies, and the development of conjugates based on large and small delivery vehicles. Neri and colleagues discuss the development of drug conjugates for cancer therapy, focusing on current and future opportunities to improve tumor-targeting efficacy with small molecule–drug conjugates and combination therapies.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1494-1504"},"PeriodicalIF":28.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040771","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 : 2025-09-10DOI: 10.1038/s43018-025-01051-9
Gabrielle Brewer
{"title":"Gut check for CAR T success","authors":"Gabrielle Brewer","doi":"10.1038/s43018-025-01051-9","DOIUrl":"10.1038/s43018-025-01051-9","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1484-1484"},"PeriodicalIF":28.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033677","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 : 2025-09-04DOI: 10.1038/s43018-025-01030-0
We developed paclitaxome-2, an optimized version of the sphingomyelin-derived paclitaxel nanovesicle paclitaxome. Leveraging the cationization-enabled transcytosis machinery boosted tumor penetration, and incorporating CD47 ‘self’ peptide masking minimized phagocytosis. Co-delivery of gemcitabine or carboplatin improved therapeutic outcomes in advanced pancreatic cancer and post-surgical triple-negative breast cancer in mouse models.
{"title":"A sphingolipid-derived paclitaxel nanovesicle for improved cancer therapy","authors":"","doi":"10.1038/s43018-025-01030-0","DOIUrl":"10.1038/s43018-025-01030-0","url":null,"abstract":"We developed paclitaxome-2, an optimized version of the sphingomyelin-derived paclitaxel nanovesicle paclitaxome. Leveraging the cationization-enabled transcytosis machinery boosted tumor penetration, and incorporating CD47 ‘self’ peptide masking minimized phagocytosis. Co-delivery of gemcitabine or carboplatin improved therapeutic outcomes in advanced pancreatic cancer and post-surgical triple-negative breast cancer in mouse models.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1619-1620"},"PeriodicalIF":28.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001031","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 : 2025-09-02DOI: 10.1038/s43018-025-01034-w
Antti S. Rannikko
Prostate MRI has emerged as a way to improve accuracy in prostate cancer diagnostics. However, the subjectivity of assessments remains a challenge. New research shows that AI can help in this task and serve as a tool to improve MRI-based prediction of prostate cancer aggressiveness.
{"title":"Artificial intelligence for prostate cancer diagnostics","authors":"Antti S. Rannikko","doi":"10.1038/s43018-025-01034-w","DOIUrl":"10.1038/s43018-025-01034-w","url":null,"abstract":"Prostate MRI has emerged as a way to improve accuracy in prostate cancer diagnostics. However, the subjectivity of assessments remains a challenge. New research shows that AI can help in this task and serve as a tool to improve MRI-based prediction of prostate cancer aggressiveness.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1613-1614"},"PeriodicalIF":28.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961899","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 : 2025-09-02DOI: 10.1038/s43018-025-01041-x
Lizhi Shao, Chao Liang, Ye Yan, Haibin Zhu, Xiaoming Jiang, Meiling Bao, Pan Zang, Xiazi Huang, Hongyu Zhou, Pei Nie, Liang Wang, Jie Li, Shudong Zhang, Shancheng Ren
Prostate cancer is a leading health concern for men, yet current clinical assessments of tumor aggressiveness rely on invasive procedures that often lead to inconsistencies. There remains a critical need for accurate, noninvasive diagnosis and grading methods. Here we developed a foundation model trained on multiparametric magnetic resonance imaging (MRI) and paired pathology data for noninvasive diagnosis and grading of prostate cancer. Our model, MRI-based Predicted Transformer for Prostate Cancer (MRI-PTPCa), was trained under contrastive learning on nearly 1.3 million image–pathology pairs from over 5,500 patients in discovery, modeling, external and prospective cohorts. During real-world testing, prediction of MRI-PTPCa demonstrated consistency with pathology and superior performance (area under the curve above 0.978; grading accuracy 89.1%) compared with clinical measures and other prediction models. This work introduces a scalable, noninvasive approach to prostate cancer diagnosis and grading, offering a robust tool to support clinical decision-making while reducing reliance on biopsies. Shao et al. developed an MRI–pathology-based foundation model to assess the pathology of prostate cancer for diagnosis and grading of tumors. The model is noninvasive and outperforms current pathological assessments.
{"title":"An MRI–pathology foundation model for noninvasive diagnosis and grading of prostate cancer","authors":"Lizhi Shao, Chao Liang, Ye Yan, Haibin Zhu, Xiaoming Jiang, Meiling Bao, Pan Zang, Xiazi Huang, Hongyu Zhou, Pei Nie, Liang Wang, Jie Li, Shudong Zhang, Shancheng Ren","doi":"10.1038/s43018-025-01041-x","DOIUrl":"10.1038/s43018-025-01041-x","url":null,"abstract":"Prostate cancer is a leading health concern for men, yet current clinical assessments of tumor aggressiveness rely on invasive procedures that often lead to inconsistencies. There remains a critical need for accurate, noninvasive diagnosis and grading methods. Here we developed a foundation model trained on multiparametric magnetic resonance imaging (MRI) and paired pathology data for noninvasive diagnosis and grading of prostate cancer. Our model, MRI-based Predicted Transformer for Prostate Cancer (MRI-PTPCa), was trained under contrastive learning on nearly 1.3 million image–pathology pairs from over 5,500 patients in discovery, modeling, external and prospective cohorts. During real-world testing, prediction of MRI-PTPCa demonstrated consistency with pathology and superior performance (area under the curve above 0.978; grading accuracy 89.1%) compared with clinical measures and other prediction models. This work introduces a scalable, noninvasive approach to prostate cancer diagnosis and grading, offering a robust tool to support clinical decision-making while reducing reliance on biopsies. Shao et al. developed an MRI–pathology-based foundation model to assess the pathology of prostate cancer for diagnosis and grading of tumors. The model is noninvasive and outperforms current pathological assessments.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1621-1637"},"PeriodicalIF":28.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961810","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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