Pub Date : 2025-08-18DOI: 10.1038/s43018-025-01037-7
Jessalyn M. Ubellacker, Scott J. Dixon
Ferroptosis is a nonapoptotic form of cell death characterized by lethal membrane lipid peroxidation. This mechanism was first characterized in cancer cells well over a decade ago, and there is much enthusiasm for the concept that certain cancers may be treated by inducing ferroptosis. However, therapies that engage ferroptosis have yet to enter clinical testing. In this Review, we highlight the gap between our rapidly expanding knowledge of the ferroptosis mechanism and its translation into cancer therapies. We discuss the known challenges that may be slowing ferroptosis therapies from reaching the clinic. Ubellacker and Dixon summarize the latest discoveries on ferroptosis in cancer, covering the molecular and cellular pathways underlying sensitivity and resistance to this type of cell death, as well as potential translational applications in cancer therapeutics.
{"title":"Prospects for ferroptosis therapies in cancer","authors":"Jessalyn M. Ubellacker, Scott J. Dixon","doi":"10.1038/s43018-025-01037-7","DOIUrl":"10.1038/s43018-025-01037-7","url":null,"abstract":"Ferroptosis is a nonapoptotic form of cell death characterized by lethal membrane lipid peroxidation. This mechanism was first characterized in cancer cells well over a decade ago, and there is much enthusiasm for the concept that certain cancers may be treated by inducing ferroptosis. However, therapies that engage ferroptosis have yet to enter clinical testing. In this Review, we highlight the gap between our rapidly expanding knowledge of the ferroptosis mechanism and its translation into cancer therapies. We discuss the known challenges that may be slowing ferroptosis therapies from reaching the clinic. Ubellacker and Dixon summarize the latest discoveries on ferroptosis in cancer, covering the molecular and cellular pathways underlying sensitivity and resistance to this type of cell death, as well as potential translational applications in cancer therapeutics.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1326-1336"},"PeriodicalIF":28.5,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874210","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 : 2025-08-08DOI: 10.1038/s43018-025-01006-0
Elizabeth D. Lightbody, Romanos Sklavenitis-Pistofidis, Ting Wu, Junko Tsuji, Danielle T. Firer, Michael P. Agius, Ankit K. Dutta, Hadley Barr, Sungjae Kim, Jean-Baptiste Alberge, Sarah Nersesian, Tim Coorens, Nicholas J. Haradhvala, Nang Kham Su, Cody J. Boehner, Michelle P. Aranha, Mahshid Rahmat, Yoshinobu Konishi, Laura Hevenor, Katherine Towle, Erica Horowitz, Jacqueline Perry, Maya Davis, Kelly A. Walsh, Christian J. Cea-Curry, Grace Fleming, Michael E. Vinyard, Daniel Heilpern-Mallory, Habib El-Khoury, Annie Cowan, John E. Ready, Catherine R. Marinac, Gad Getz, Irene M. Ghobrial
Multiple myeloma is a bone marrow (BM) plasma cell malignancy preceded by precursor conditions. BM biopsies are conducted infrequently and can yield inconclusive results due to technical limitations. Profiling circulating tumor cells (CTCs) may enable noninvasive routine clinical assessments but remains challenging. Here, to address this, we describe a single-cell sequencing workflow to interrogate few tumor cells (SWIFT-seq), and employ single-cell RNA sequencing and B cell receptor sequencing on paired BM and CTCs from 101 patients and healthy donors. We establish a sequencing-based CTC enumeration strategy and develop a CTC classifier to infer cytogenetic abnormalities. Additionally, we leverage expression profiling to measure tumor proliferative index in CTCs, and demonstrate that clonal dynamics can be captured in CTCs. Last, we propose a circulatory dynamics model whereby tumor burden, proliferation, cytogenetics and a circulatory capacity signature influence CTC burden. Overall, SWIFT-seq may advance blood-based myeloma diagnostics, surveillance and prognostication, and reveal biological mechanisms of tumor dissemination. Lightbody et al. present SWIFT-seq, a single-cell RNA sequencing approach to profile circulating tumor cells from patients with multiple myeloma and its precursor conditions and leverage it to derive clinical and biological insights into the disease.
{"title":"SWIFT-seq enables comprehensive single-cell transcriptomic profiling of circulating tumor cells in multiple myeloma and its precursors","authors":"Elizabeth D. Lightbody, Romanos Sklavenitis-Pistofidis, Ting Wu, Junko Tsuji, Danielle T. Firer, Michael P. Agius, Ankit K. Dutta, Hadley Barr, Sungjae Kim, Jean-Baptiste Alberge, Sarah Nersesian, Tim Coorens, Nicholas J. Haradhvala, Nang Kham Su, Cody J. Boehner, Michelle P. Aranha, Mahshid Rahmat, Yoshinobu Konishi, Laura Hevenor, Katherine Towle, Erica Horowitz, Jacqueline Perry, Maya Davis, Kelly A. Walsh, Christian J. Cea-Curry, Grace Fleming, Michael E. Vinyard, Daniel Heilpern-Mallory, Habib El-Khoury, Annie Cowan, John E. Ready, Catherine R. Marinac, Gad Getz, Irene M. Ghobrial","doi":"10.1038/s43018-025-01006-0","DOIUrl":"10.1038/s43018-025-01006-0","url":null,"abstract":"Multiple myeloma is a bone marrow (BM) plasma cell malignancy preceded by precursor conditions. BM biopsies are conducted infrequently and can yield inconclusive results due to technical limitations. Profiling circulating tumor cells (CTCs) may enable noninvasive routine clinical assessments but remains challenging. Here, to address this, we describe a single-cell sequencing workflow to interrogate few tumor cells (SWIFT-seq), and employ single-cell RNA sequencing and B cell receptor sequencing on paired BM and CTCs from 101 patients and healthy donors. We establish a sequencing-based CTC enumeration strategy and develop a CTC classifier to infer cytogenetic abnormalities. Additionally, we leverage expression profiling to measure tumor proliferative index in CTCs, and demonstrate that clonal dynamics can be captured in CTCs. Last, we propose a circulatory dynamics model whereby tumor burden, proliferation, cytogenetics and a circulatory capacity signature influence CTC burden. Overall, SWIFT-seq may advance blood-based myeloma diagnostics, surveillance and prognostication, and reveal biological mechanisms of tumor dissemination. Lightbody et al. present SWIFT-seq, a single-cell RNA sequencing approach to profile circulating tumor cells from patients with multiple myeloma and its precursor conditions and leverage it to derive clinical and biological insights into the disease.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 9","pages":"1595-1611"},"PeriodicalIF":28.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804379","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 : 2025-08-07DOI: 10.1038/s43018-025-01025-x
Adam J. Grippin, DaeYong Lee, Eileen E. Parkes, Wen Jiang, Betty Y. S. Kim
Although the first generation of cancer immunotherapeutics produced unprecedented improvements in clinical outcomes for individuals with cancer, novel strategies to increase treatment specificity, delivery efficiency and pharmacokinetics are still needed. In this Review, we describe the potential advantages and current limitations of nanomaterials for cancer immunotherapy and highlight rational uses of nanosystems to generate potent and durable antitumor immune responses. We close with a review of the current state of clinical development of nanomedicine for cancer immunotherapy. Kim and colleagues provide an overview of the current state of the art of nanomaterials and their application in immuno-oncology, discussing preclinical development and the clinical landscape.
{"title":"Nanotechnology for immuno-oncology","authors":"Adam J. Grippin, DaeYong Lee, Eileen E. Parkes, Wen Jiang, Betty Y. S. Kim","doi":"10.1038/s43018-025-01025-x","DOIUrl":"10.1038/s43018-025-01025-x","url":null,"abstract":"Although the first generation of cancer immunotherapeutics produced unprecedented improvements in clinical outcomes for individuals with cancer, novel strategies to increase treatment specificity, delivery efficiency and pharmacokinetics are still needed. In this Review, we describe the potential advantages and current limitations of nanomaterials for cancer immunotherapy and highlight rational uses of nanosystems to generate potent and durable antitumor immune responses. We close with a review of the current state of clinical development of nanomedicine for cancer immunotherapy. Kim and colleagues provide an overview of the current state of the art of nanomaterials and their application in immuno-oncology, discussing preclinical development and the clinical landscape.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1311-1325"},"PeriodicalIF":28.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799708","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 : 2025-08-01DOI: 10.1038/s43018-025-01019-9
In metastatic, immunologically ‘cold’ non-small cell lung cancer, the combination of radiation therapy and immune checkpoint inhibition (ICI) demonstrates heightened anti-tumor immune responses at non-irradiated sites and improved clinical responses compared with ICI alone. Radio-immunotherapy holds promise for patients with ICI-refractory lung cancer.
{"title":"Improved immune responses in lung cancer with radiotherapy and immune checkpoint inhibition","authors":"","doi":"10.1038/s43018-025-01019-9","DOIUrl":"10.1038/s43018-025-01019-9","url":null,"abstract":"In metastatic, immunologically ‘cold’ non-small cell lung cancer, the combination of radiation therapy and immune checkpoint inhibition (ICI) demonstrates heightened anti-tumor immune responses at non-irradiated sites and improved clinical responses compared with ICI alone. Radio-immunotherapy holds promise for patients with ICI-refractory lung cancer.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1617-1618"},"PeriodicalIF":28.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765024","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 : 2025-07-30DOI: 10.1038/s43018-025-01028-8
Tiffanie Chouleur
{"title":"Coordination of cell subsets in health and cancer","authors":"Tiffanie Chouleur","doi":"10.1038/s43018-025-01028-8","DOIUrl":"10.1038/s43018-025-01028-8","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1299-1299"},"PeriodicalIF":28.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753875","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 : 2025-07-23DOI: 10.1038/s43018-025-01036-8
Giulia Petroni, Claudia Galassi, Kenneth H. Gouin III, Hsiang-Han Chen, Aitziber Buqué, Norma Bloy, Takahiro Yamazaki, Ai Sato, Manuel Beltrán-Visiedo, Ginevra Campia, Carlos Jiménez-Cortegana, Aagam Shah, Alexander Kirchmair, Chiara Massa, Claudia Wickenhauser, Carlos Eduardo de Andrea, Belén Navarro-Rubio, Irantzu Serrano-Mendioroz, Esther Navarro Manzano, Alexandra M. Satty, Brady Rippon, Francesca Finotello, Zlatko Trajanoski, Xi Kathy Zhou, Joseph M. Scandura, Elena García-Martínez, Francisco Ayala de la Peña, María Esperanza Rodríguez-Ruiz, Barbara Seliger, Víctor Sánchez-Margalet, Luis de la Cruz-Merino, Reva K. Basho, Stephen L. Shiao, Heather L. McArthur, Silvia C. Formenti, Simon R. V. Knott, Lorenzo Galluzzi
{"title":"Author Correction: IL-17A-secreting γδ T cells promote resistance to CDK4/CDK6 inhibitors in HR+HER2− breast cancer via CX3CR1+ macrophages","authors":"Giulia Petroni, Claudia Galassi, Kenneth H. Gouin III, Hsiang-Han Chen, Aitziber Buqué, Norma Bloy, Takahiro Yamazaki, Ai Sato, Manuel Beltrán-Visiedo, Ginevra Campia, Carlos Jiménez-Cortegana, Aagam Shah, Alexander Kirchmair, Chiara Massa, Claudia Wickenhauser, Carlos Eduardo de Andrea, Belén Navarro-Rubio, Irantzu Serrano-Mendioroz, Esther Navarro Manzano, Alexandra M. Satty, Brady Rippon, Francesca Finotello, Zlatko Trajanoski, Xi Kathy Zhou, Joseph M. Scandura, Elena García-Martínez, Francisco Ayala de la Peña, María Esperanza Rodríguez-Ruiz, Barbara Seliger, Víctor Sánchez-Margalet, Luis de la Cruz-Merino, Reva K. Basho, Stephen L. Shiao, Heather L. McArthur, Silvia C. Formenti, Simon R. V. Knott, Lorenzo Galluzzi","doi":"10.1038/s43018-025-01036-8","DOIUrl":"10.1038/s43018-025-01036-8","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1754-1754"},"PeriodicalIF":28.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-025-01036-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699096","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 : 2025-07-23DOI: 10.1038/s43018-025-01035-9
Sohinee Bhattacharyya, Chet Oon, Luis Diaz, Holly Sandborg, Erin S. Stempinski, Michelle Saoi, Terry K. Morgan, Claudia S. López, Justin R. Cross, Mara H. Sherman
{"title":"Author Correction: Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression","authors":"Sohinee Bhattacharyya, Chet Oon, Luis Diaz, Holly Sandborg, Erin S. Stempinski, Michelle Saoi, Terry K. Morgan, Claudia S. López, Justin R. Cross, Mara H. Sherman","doi":"10.1038/s43018-025-01035-9","DOIUrl":"10.1038/s43018-025-01035-9","url":null,"abstract":"","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 8","pages":"1477-1477"},"PeriodicalIF":28.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699095","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 : 2025-07-22DOI: 10.1038/s43018-025-01018-w
Justin Huang, Willemijn S. M. E. Theelen, Zineb Belcaid, Mimi Najjar, Daphne van der Geest, Dipika Singh, Christopher Cherry, Archana Balan, James R. White, Jaime Wehr, Rachel Karchin, Noushin Niknafs, Michel M. van den Heuvel, Victor E. Velculescu, Kellie N. Smith, Paul Baas, Valsamo Anagnostou
The abscopal effects of radiation may sensitize immunologically cold tumors to immune checkpoint inhibition. We investigated the immunostimulatory effects of radiotherapy leveraging multiomic analyses of serial tissue and blood biospecimens (n = 293) from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer ( NCT02492568 ). Participants with immunologically cold tumors (low tumor mutation burden, null programmed death ligand 1 expression or Wnt pathway mutations) had significantly longer progression-free survival in the SBRT arm. Induction of interferon-γ, interferon-α and antigen processing and presentation gene sets was significantly enriched after SBRT in nonirradiated tumor sites. Significant on-therapy expansions of new and pre-existing T cell clones in both the tumor (abscopal) and the blood (systemic) compartments were noted alongside clonal neoantigen-reactive autologous T cell responses in participants with long-term survival after radioimmunotherapy. These findings support the systemic immunomodulatory and antitumor effects of radioimmunotherapy and may open a therapeutic window of opportunity to overcome immunotherapy resistance. Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.
{"title":"Combination of pembrolizumab and radiotherapy induces systemic antitumor immune responses in immunologically cold non-small cell lung cancer","authors":"Justin Huang, Willemijn S. M. E. Theelen, Zineb Belcaid, Mimi Najjar, Daphne van der Geest, Dipika Singh, Christopher Cherry, Archana Balan, James R. White, Jaime Wehr, Rachel Karchin, Noushin Niknafs, Michel M. van den Heuvel, Victor E. Velculescu, Kellie N. Smith, Paul Baas, Valsamo Anagnostou","doi":"10.1038/s43018-025-01018-w","DOIUrl":"10.1038/s43018-025-01018-w","url":null,"abstract":"The abscopal effects of radiation may sensitize immunologically cold tumors to immune checkpoint inhibition. We investigated the immunostimulatory effects of radiotherapy leveraging multiomic analyses of serial tissue and blood biospecimens (n = 293) from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer ( NCT02492568 ). Participants with immunologically cold tumors (low tumor mutation burden, null programmed death ligand 1 expression or Wnt pathway mutations) had significantly longer progression-free survival in the SBRT arm. Induction of interferon-γ, interferon-α and antigen processing and presentation gene sets was significantly enriched after SBRT in nonirradiated tumor sites. Significant on-therapy expansions of new and pre-existing T cell clones in both the tumor (abscopal) and the blood (systemic) compartments were noted alongside clonal neoantigen-reactive autologous T cell responses in participants with long-term survival after radioimmunotherapy. These findings support the systemic immunomodulatory and antitumor effects of radioimmunotherapy and may open a therapeutic window of opportunity to overcome immunotherapy resistance. Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.","PeriodicalId":18885,"journal":{"name":"Nature cancer","volume":"6 10","pages":"1676-1692"},"PeriodicalIF":28.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s43018-025-01018-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691028","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}
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