Pub Date : 2024-09-02DOI: 10.1038/s41568-024-00737-z
Mariangela Russo, Mengnuo Chen, Elisa Mariella, Haoning Peng, Sumaiyah K. Rehman, Elena Sancho, Alberto Sogari, Tzen S. Toh, Nathalie Q. Balaban, Eduard Batlle, Rene Bernards, Mathew J. Garnett, Matthew Hangauer, Eleonora Leucci, Jean-Christophe Marine, Catherine A. O’Brien, Yaara Oren, E. Elizabeth Patton, Caroline Robert, Susan M. Rosenberg, Shensi Shen, Alberto Bardelli
The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumour. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumour microenvironment, including their potential to evade immune surveillance, remain to be discovered. Finally, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavours in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication. Resistance to therapy remains the biggest challenge to achieving cures in patients with cancer. In this Roadmap, Russo et al. overview the field of cancer drug-tolerant persister cells providing paths to advance our understanding of their biology with innovative technologies and recommend strategies to therapeutically target them to ensure that more prolonged responses are achieved in patients with cancer.
{"title":"Cancer drug-tolerant persister cells: from biological questions to clinical opportunities","authors":"Mariangela Russo, Mengnuo Chen, Elisa Mariella, Haoning Peng, Sumaiyah K. Rehman, Elena Sancho, Alberto Sogari, Tzen S. Toh, Nathalie Q. Balaban, Eduard Batlle, Rene Bernards, Mathew J. Garnett, Matthew Hangauer, Eleonora Leucci, Jean-Christophe Marine, Catherine A. O’Brien, Yaara Oren, E. Elizabeth Patton, Caroline Robert, Susan M. Rosenberg, Shensi Shen, Alberto Bardelli","doi":"10.1038/s41568-024-00737-z","DOIUrl":"10.1038/s41568-024-00737-z","url":null,"abstract":"The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumour. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumour microenvironment, including their potential to evade immune surveillance, remain to be discovered. Finally, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavours in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication. Resistance to therapy remains the biggest challenge to achieving cures in patients with cancer. In this Roadmap, Russo et al. overview the field of cancer drug-tolerant persister cells providing paths to advance our understanding of their biology with innovative technologies and recommend strategies to therapeutically target them to ensure that more prolonged responses are achieved in patients with cancer.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"694-717"},"PeriodicalIF":72.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1038/s41568-024-00747-x
Gabriel Lopez, Santhosshi Narayanan, Lorenzo Cohen
{"title":"Author Correction: Integrative medicine in oncology: redefining the standard of care","authors":"Gabriel Lopez, Santhosshi Narayanan, Lorenzo Cohen","doi":"10.1038/s41568-024-00747-x","DOIUrl":"10.1038/s41568-024-00747-x","url":null,"abstract":"","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 11","pages":"822-822"},"PeriodicalIF":72.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41568-024-00747-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1038/s41568-024-00736-0
Sophie Guelfi, Kairbaan Hodivala-Dilke, Gabriele Bergers
As angiogenesis was recognized as a core hallmark of cancer growth and survival, several strategies have been implemented to target the tumour vasculature. Yet to date, attempts have rarely been so diverse, ranging from vessel growth inhibition and destruction to vessel normalization, reprogramming and vessel growth promotion. Some of these strategies, combined with standard of care, have translated into improved cancer therapies, but their successes are constrained to certain cancer types. This Review provides an overview of these vascular targeting approaches and puts them into context based on our subsequent improved understanding of the tumour vasculature as an integral part of the tumour microenvironment with which it is functionally interlinked. This new knowledge has already led to dual targeting of the vascular and immune cell compartments and sets the scene for future investigations of possible alternative approaches that consider the vascular link with other tumour microenvironment components for improved cancer therapy. Various strategies have been proposed and implemented to target the tumour vasculature, which supports tumour growth and progression. However, to date they have had variable success. Guelfi et al. describe some of these approaches and discuss how our increased understanding of the interactions between tumour vessels and the immune compartment could help generate combination therapies that provide durable responses in patients with cancer.
{"title":"Targeting the tumour vasculature: from vessel destruction to promotion","authors":"Sophie Guelfi, Kairbaan Hodivala-Dilke, Gabriele Bergers","doi":"10.1038/s41568-024-00736-0","DOIUrl":"10.1038/s41568-024-00736-0","url":null,"abstract":"As angiogenesis was recognized as a core hallmark of cancer growth and survival, several strategies have been implemented to target the tumour vasculature. Yet to date, attempts have rarely been so diverse, ranging from vessel growth inhibition and destruction to vessel normalization, reprogramming and vessel growth promotion. Some of these strategies, combined with standard of care, have translated into improved cancer therapies, but their successes are constrained to certain cancer types. This Review provides an overview of these vascular targeting approaches and puts them into context based on our subsequent improved understanding of the tumour vasculature as an integral part of the tumour microenvironment with which it is functionally interlinked. This new knowledge has already led to dual targeting of the vascular and immune cell compartments and sets the scene for future investigations of possible alternative approaches that consider the vascular link with other tumour microenvironment components for improved cancer therapy. Various strategies have been proposed and implemented to target the tumour vasculature, which supports tumour growth and progression. However, to date they have had variable success. Guelfi et al. describe some of these approaches and discuss how our increased understanding of the interactions between tumour vessels and the immune compartment could help generate combination therapies that provide durable responses in patients with cancer.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"655-675"},"PeriodicalIF":72.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-27DOI: 10.1038/s41568-024-00739-x
Marzyeh Ghassemi, Alexander Gusev
{"title":"Limiting bias in AI models for improved and equitable cancer care.","authors":"Marzyeh Ghassemi, Alexander Gusev","doi":"10.1038/s41568-024-00739-x","DOIUrl":"https://doi.org/10.1038/s41568-024-00739-x","url":null,"abstract":"","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":" ","pages":""},"PeriodicalIF":72.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1038/s41568-024-00741-3
Gabrielle Brewer
Inflammation is well established as a risk factor for cancer development in the gut. In this study, Fesneau et al. identify a specific immune cell population, derived from T helper 17 (TH17) cells, that can initiate intestinal cancer.
炎症是肠道癌症发生的一个风险因素，这一点已得到公认。在这项研究中，Fesneau 等人发现了一种可引发肠癌的特定免疫细胞群，它来自 T 辅助细胞 17（TH17）。
{"title":"Thelpers? More like Ttroublemakers","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00741-3","DOIUrl":"10.1038/s41568-024-00741-3","url":null,"abstract":"Inflammation is well established as a risk factor for cancer development in the gut. In this study, Fesneau et al. identify a specific immune cell population, derived from T helper 17 (TH17) cells, that can initiate intestinal cancer.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"651-651"},"PeriodicalIF":72.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.1038/s41568-024-00735-1
Gabriel Lopez, Santhosshi Narayanan, Lorenzo Cohen
Integrative medicine incorporated alongside cancer care, referred to as integrative oncology, is an evidence-informed field with established clinical guidelines. Although integrative oncology improves patient outcomes, it is inconsistently provided to patients. To align with best practices, it is necessary to increase awareness of integrative oncology, improve access to treatments, and provide consistent financial healthcare coverage.
{"title":"Integrative medicine in oncology: redefining the standard of care","authors":"Gabriel Lopez, Santhosshi Narayanan, Lorenzo Cohen","doi":"10.1038/s41568-024-00735-1","DOIUrl":"10.1038/s41568-024-00735-1","url":null,"abstract":"Integrative medicine incorporated alongside cancer care, referred to as integrative oncology, is an evidence-informed field with established clinical guidelines. Although integrative oncology improves patient outcomes, it is inconsistently provided to patients. To align with best practices, it is necessary to increase awareness of integrative oncology, improve access to treatments, and provide consistent financial healthcare coverage.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 11","pages":"739-740"},"PeriodicalIF":72.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1038/s41568-024-00733-3
Jiwon Koh, Seock-Ah Im
In this Journal Club, Koh and Im discuss a study demonstrating the unique evolutionary trajectory of breast cancers harbouring the common driver alteration der(1;16).
在本期 "期刊俱乐部 "中，Koh 和 Im 讨论了一项研究，该研究展示了携带常见驱动基因改变 der(1;16) 的乳腺癌的独特进化轨迹。
{"title":"Tracing the evolutionary history of breast cancer","authors":"Jiwon Koh, Seock-Ah Im","doi":"10.1038/s41568-024-00733-3","DOIUrl":"10.1038/s41568-024-00733-3","url":null,"abstract":"In this Journal Club, Koh and Im discuss a study demonstrating the unique evolutionary trajectory of breast cancers harbouring the common driver alteration der(1;16).","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"653-653"},"PeriodicalIF":72.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1038/s41568-024-00728-0
Jean-Luc Teillaud, Ana Houel, Marylou Panouillot, Clémence Riffard, Marie-Caroline Dieu-Nosjean
Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment. TLS have also garnered considerable interest as a predictive biomarker of the response to antitumour therapies, including immune checkpoint blockade and, possibly, chemotherapy. However, several important questions still remain regarding the definition of TLS in terms of both their cellular composition and functions. Here, we summarize the current views on the composition of TLS at different stages of their development. We also discuss the role of B cells and T cells associated with TLS and their dialogue in mounting antibody and cellular antitumour responses, as well as some of the various mechanisms that negatively regulate antitumour activity of TLS. The prognostic value of TLS to the clinical outcome of patients with cancer and the relationship between TLS and the response to therapy are then addressed. Finally, we present some preclinical evidence that favours the idea that manipulating the formation and function of TLS could lead to a potent next-generation cancer immunotherapy. Transient ectopic lymphoid structures known as tertiary lymphoid structures (TLS) have been observed in many solid tumour types. In this Review, Teillaud et al. discuss how these TLS potentially orchestrate immune responses against tumours locally and are positively associated with prognosis and response to immune checkpoint inhibitors. The authors also outline how preclinical studies are highlighting the potential to manipulate the formation and function of TLS as a novel form of immunotherapy.
{"title":"Tertiary lymphoid structures in anticancer immunity","authors":"Jean-Luc Teillaud, Ana Houel, Marylou Panouillot, Clémence Riffard, Marie-Caroline Dieu-Nosjean","doi":"10.1038/s41568-024-00728-0","DOIUrl":"10.1038/s41568-024-00728-0","url":null,"abstract":"Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment. TLS have also garnered considerable interest as a predictive biomarker of the response to antitumour therapies, including immune checkpoint blockade and, possibly, chemotherapy. However, several important questions still remain regarding the definition of TLS in terms of both their cellular composition and functions. Here, we summarize the current views on the composition of TLS at different stages of their development. We also discuss the role of B cells and T cells associated with TLS and their dialogue in mounting antibody and cellular antitumour responses, as well as some of the various mechanisms that negatively regulate antitumour activity of TLS. The prognostic value of TLS to the clinical outcome of patients with cancer and the relationship between TLS and the response to therapy are then addressed. Finally, we present some preclinical evidence that favours the idea that manipulating the formation and function of TLS could lead to a potent next-generation cancer immunotherapy. Transient ectopic lymphoid structures known as tertiary lymphoid structures (TLS) have been observed in many solid tumour types. In this Review, Teillaud et al. discuss how these TLS potentially orchestrate immune responses against tumours locally and are positively associated with prognosis and response to immune checkpoint inhibitors. The authors also outline how preclinical studies are highlighting the potential to manipulate the formation and function of TLS as a novel form of immunotherapy.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 9","pages":"629-646"},"PeriodicalIF":72.5,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1038/s41568-024-00732-4
Daniela Senft
In a recent study published in Nature, lactate has been identified as a key player in enhancing DNA repair mechanisms in gastric cancer by promoting lactylation of DNA repair proteins, leading to chemotherapy resistance.
最近发表在《自然》杂志上的一项研究发现，乳酸盐通过促进 DNA 修复蛋白的乳化作用，成为增强胃癌 DNA 修复机制的关键因素，从而导致化疗耐药性。
{"title":"Lactate promotes DNA repair","authors":"Daniela Senft","doi":"10.1038/s41568-024-00732-4","DOIUrl":"10.1038/s41568-024-00732-4","url":null,"abstract":"In a recent study published in Nature, lactate has been identified as a key player in enhancing DNA repair mechanisms in gastric cancer by promoting lactylation of DNA repair proteins, leading to chemotherapy resistance.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 9","pages":"593-593"},"PeriodicalIF":72.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1038/s41568-024-00738-y
Frank Dubois, Nikos Sidiropoulos, Joachim Weischenfeldt, Rameen Beroukhim
{"title":"Publisher Correction: Structural variations in cancer and the 3D genome","authors":"Frank Dubois, Nikos Sidiropoulos, Joachim Weischenfeldt, Rameen Beroukhim","doi":"10.1038/s41568-024-00738-y","DOIUrl":"10.1038/s41568-024-00738-y","url":null,"abstract":"","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"735-735"},"PeriodicalIF":72.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41568-024-00738-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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