Nature Reviews Cancer最新文献_第2页

Mechanisms and treatment of cancer therapy-induced peripheral and central neurotoxicity 癌症治疗诱导的周围和中枢神经毒性的机制和治疗

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-09-09 DOI: 10.1038/s41568-025-00863-2

Philipp Karschnia, Thomas A. Nelson, Jorg Dietrich

{"title":"Mechanisms and treatment of cancer therapy-induced peripheral and central neurotoxicity","authors":"Philipp Karschnia, Thomas A. Nelson, Jorg Dietrich","doi":"10.1038/s41568-025-00863-2","DOIUrl":"https://doi.org/10.1038/s41568-025-00863-2","url":null,"abstract":"Neurotoxicity is a common and potentially severe adverse effect from conventional and novel cancer therapy. The mechanisms that underlie clinical symptoms of central and peripheral nervous system injury remain incompletely understood. For conventional cytotoxic chemotherapy or radiotherapy, direct toxicities to brain structures and neurovascular damage may result in myelin degradation and impaired neurogenesis, which eventually translates into delayed neurodegeneration accompanied by cognitive symptoms. Chemotherapy-induced peripheral neuropathy is one of the most prevalent adverse events of chemotherapy, seen specifically with platinum- and taxane-based regimens, vinca alkaloids, thalidomide and bortezomib, and is also emerging as a concerning feature of novel targeted therapies and immunotherapies. In patients treated with molecularly targeted compounds or immune-activating agents, on-target but off-tumour effects and systemic inflammation characterize a distinct clinical profile with predominantly acute neurological symptoms with a phenotype defined by the specific antigen target. The development of mechanistically driven treatment strategies for both central and peripheral nervous system injury from cancer therapies is a major unmet medical need. Clinical trials designed to test pharmacotherapeutic interventions (including anti-dementia drugs or cognitive stimulants) for cognitive symptoms after conventional chemotherapy have produced conflicting results. In the case of acute neurotoxic adverse events from immunotherapies, reversal of T cell expansion together with drugs targeting specific pro-inflammatory interleukins have shown beneficial effects in selected patients. Large clinical trials to test novel strategies and pharmacotherapeutic interventions for acute or delayed neurotoxicity are ongoing. Informed by data derived from clinical trials and preclinical models, promising treatment strategies are on the horizon.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"65 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017231","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}

引用次数: 0

Aggregating premalignancy 聚合初癌

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-09-08 DOI: 10.1038/s41568-025-00876-x

Daniela Senft

引用次数: 0

Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer 揭示癌症中衰老肿瘤微环境的遗传学和表观遗传学

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-09-08 DOI: 10.1038/s41568-025-00868-x

Hariharan Easwaran, Ashani T. Weeraratna

{"title":"Unravelling the genetics and epigenetics of the ageing tumour microenvironment in cancer","authors":"Hariharan Easwaran, Ashani T. Weeraratna","doi":"10.1038/s41568-025-00868-x","DOIUrl":"https://doi.org/10.1038/s41568-025-00868-x","url":null,"abstract":"Somatic mutations in several genes, including key oncogenes and tumour suppressor genes, are present from early life and can accumulate as an individual ages, indicating that the potential for cancer is present and growing throughout life. However, the risk of developing cancer rises sharply after 50–60 years of age, suggesting that the ability of these mutations to undergo clonal expansion and drive cancer development is dependent on the progressive changes in the epigenome and microenvironment that occur during ageing. Epigenetic changes, including DNA methylation and histone modifications, can drive various hallmarks of ageing in precancerous cells, including induction of senescence, the senescence-associated secretory phenotype, genomic instability and reduction of nuclear integrity, metabolic and inflammatory stress responses, stem cell function and differentiation potential, and redox balance. This can also alter the normal immune and stromal cells in the tissue microenvironment, which cumulatively enhances the effects of cancer driver mutations, ultimately promoting cancer development and progression in aged individuals. Unravelling these mechanisms will provide novel preventive and therapeutic strategies to limit the burden and progression of cancer in aged individuals.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"128 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017233","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}

引用次数: 0

3D chromatin architecture as a predictor of somatic mutations in cancer genomes 三维染色质结构作为癌症基因组体细胞突变的预测因子

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-09-01 DOI: 10.1038/s41568-025-00875-y

Karan Bansal, Aprotim Mazumder

引用次数: 0

The evolution of cancer and ageing: a history of constraint 癌症和衰老的演变：约束的历史

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-08-26 DOI: 10.1038/s41568-025-00861-4

João Pedro de Magalhães

{"title":"The evolution of cancer and ageing: a history of constraint","authors":"João Pedro de Magalhães","doi":"10.1038/s41568-025-00861-4","DOIUrl":"https://doi.org/10.1038/s41568-025-00861-4","url":null,"abstract":"Ageing and cancer are ubiquitous in animals. They are fundamental and generally intrinsic to multicellular life. Nonetheless, ageing and cancer rates vary widely across species and understanding their evolution and interaction is of great biological interest. Although cancer arises from uncontrolled cell proliferation, ageing involves cell loss and degeneration, making them seemingly opposite yet interconnected processes. Because cancer can affect young individuals, natural selection will favour the evolution of cancer resistance over processes that maintain health in later life. As such, I propose that species evolve longer lifespans under the constraints imposed by the need to reduce cancer risk. Mechanisms that suppress cancer, such as telomere shortening and cellular senescence, may inadvertently promote ageing by limiting cell proliferation and tissue regeneration. Selection for tumour suppression may also impact stem cell ageing and contribute to the limited ability of adult tissues to regenerate. Overall, although cancer resistance is essential for the evolution of longevity, tumour suppression mechanisms may also contribute to ageing-related tissue degeneration and functional decline. Studying the trade-offs between the evolution of tumour suppression processes and their impact later in life may provide important insights into ageing processes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"14 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899109","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}

引用次数: 0

A viral wakeup call 病毒式的警钟

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-08-21 DOI: 10.1038/s41568-025-00871-2

Gabrielle Brewer

引用次数: 0

Targeting the roots of myeloid malignancies with T cell receptors 用T细胞受体靶向髓系恶性肿瘤的根源

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-08-21 DOI: 10.1038/s41568-025-00857-0

Zsofia Foldvari, Margs S. Brennan, Aleksei Titov, Sten Eirik W. Jacobsen, Johanna Olweus

{"title":"Targeting the roots of myeloid malignancies with T cell receptors","authors":"Zsofia Foldvari, Margs S. Brennan, Aleksei Titov, Sten Eirik W. Jacobsen, Johanna Olweus","doi":"10.1038/s41568-025-00857-0","DOIUrl":"https://doi.org/10.1038/s41568-025-00857-0","url":null,"abstract":"Myeloid malignancies are clonal diseases of haematopoietic stem cell or haematopoietic progenitor cell origin, for which allogeneic haematopoietic stem cell transplantation remains the only curative treatment for most patients. However, the severe side effects and high relapse rates underscore the need for novel therapies. The success of adoptive transfer of chimeric antigen receptor (CAR) T cells targeting B cell-specific cell surface molecules in B cell cancers has not been replicated in myeloid malignancies. T cells engineered to express cancer-directed T cell receptors (TCRs) could provide an alternative, enabling targeting also of the intracellular proteome. In this Perspective, we have collated and reviewed available data from clinical trials exploiting TCR-engineered T cells for the treatment of haematological malignancies and discuss specific characteristics that make myeloid malignancies attractive candidates for TCR-based therapies. We also highlight the need to efficiently target the rare and notoriously therapy-resistant leukaemic stem cells, which represent the roots of myeloid malignancies, to achieve cures. This will require identification of novel targets and TCRs, and we discuss different target categories and strategies that can be applied towards this goal. We also highlight the importance of standardized preclinical testing and publicly available data to enable rapid identification and clinical advancement of promising TCRs towards clinical application.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"80 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899150","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}

引用次数: 0

Ageing, immune fitness and cancer 衰老，免疫健康和癌症

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-08-14 DOI: 10.1038/s41568-025-00858-z

Melissa Dolan, Kendra A. Libby, Alison E. Ringel, Peter van Galen, Sandra S. McAllister

{"title":"Ageing, immune fitness and cancer","authors":"Melissa Dolan, Kendra A. Libby, Alison E. Ringel, Peter van Galen, Sandra S. McAllister","doi":"10.1038/s41568-025-00858-z","DOIUrl":"https://doi.org/10.1038/s41568-025-00858-z","url":null,"abstract":"The immune system undergoes substantial changes throughout life, with ageing broadly impacting immune cell composition, function and regenerative capacity. Emerging evidence suggests that age-associated changes in immune fitness — the ability to respond to and eliminate infection, pathogens and malignancy while maintaining self-tolerance — reshape antitumour immunity and influence the efficacy of immunotherapies. Technological advances in high-dimensional immunoprofiling have begun to reveal the complex interplay between ageing, immune fitness and cancer biology, uncovering new therapeutic vulnerabilities and challenges. In this Review, we discuss recent insights derived from age-resolved immunoprofiling of the human tumour microenvironment, how ageing haematopoiesis affects immune cells that contribute to the microenvironment and impact cancer progression, and what is known from preclinical modelling about the functional consequences of immune ageing on tumour control. We further highlight emerging age-stratified analyses of treatment responses, which are beginning to inform hypotheses about how ageing shapes immunotherapy outcomes. Together, these perspectives provide a framework for integrating age as a critical biological variable, underscore the need to consider age in both preclinical models and clinical trial design, and identify key challenges and priorities for the field moving forward.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"742 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840045","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}

引用次数: 0

No climate havens: the expanding threat of climate change to cancer care 没有气候避风港：气候变化对癌症治疗的威胁日益扩大

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-08-14 DOI: 10.1038/s41568-025-00867-y

Leticia M. Nogueira, Renee N. Salas

引用次数: 0

The overlooked global reach of wildfire smoke: beyond local health and cancer risk 野火烟雾被忽视的全球影响：超越当地健康和癌症风险

IF 78.5 1区医学

Nature Reviews Cancer Pub Date : 2025-08-11 DOI: 10.1038/s41568-025-00865-0

Howard Lopes Ribeiro Junior, Júlio César Claudino dos Santos

{"title":"The overlooked global reach of wildfire smoke: beyond local health and cancer risk","authors":"Howard Lopes Ribeiro Junior, Júlio César Claudino dos Santos","doi":"10.1038/s41568-025-00865-0","DOIUrl":"https://doi.org/10.1038/s41568-025-00865-0","url":null,"abstract":"We read with interest the recent Comment by Weichenthal (Weichenthal, S. We cannot ignore the cancer risks of wildfires. Nat. Rev. Cancer 25, 219–220 (2025))1, which highlighted the carcinogenic risks associated with recurrent wildfires and the pressing need for public health action. We agree that wildfires are not only a local environmental issue but a growing global health crisis. However, we would like to emphasize that the geographic scope of their impact is even broader than previously discussed, with substantial consequences for public health not only in regions where the fires occur but also in areas located far from the fire epicentres, owing to long-range smoke transport.Wildfires in the Amazon and across the African continent have not only devastated ecosystems locally but have also affected distant communities through atmospheric smoke transport2,3. Observational data show that smoke from African fires can reach the Amazon basin, and fires in the Amazon, located in northern Brazil, and the Brazilian Pantanal have darkened skies and worsened air quality in Ceará, a state in northeastern Brazil4. These events are not isolated; they reflect a concerning interregional and transcontinental pattern of smoke transport with profound implications.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"8 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812897","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}

引用次数: 0