Nature Reviews Cancer最新文献_第6页

Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response 重新审视TGFβ悖论：来自hpv驱动的癌症和DNA损伤反应的见解

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-05-19 DOI: 10.1038/s41568-025-00819-6

Mary Helen Barcellos-Hoff, Sue S. Yom

{"title":"Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response","authors":"Mary Helen Barcellos-Hoff, Sue S. Yom","doi":"10.1038/s41568-025-00819-6","DOIUrl":"10.1038/s41568-025-00819-6","url":null,"abstract":"The transforming growth factor-β (TGFβ) paradox refers to the well-established role of TGFβ in suppressing cancer in healthy tissues yet promoting malignancy in established cancers. Although this positioned TGFβ inhibitors as a potential therapeutic strategy for malignancy, therapuetic blockade has failed in multiple clinical trials. The general lack of selection principles for defining which patients would most benefit from the addition of a TGFβ inhibitor has probably hindered its deployment. Here, we highlight the therapeutic potential in TGFβ regulation of DNA repair using human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) as an illustrative example. HPV inhibits TGFβ signalling, which in turn reduces DNA damage repair, ultimately conferring sensitivity to cancer treatments and thus contributing to the favourable prognosis of HPV-positive HNSCC. Here, we review the DNA repair deficit caused by a loss of TGFβ signalling and how this could be targeted to induce synthetic lethality. Moreover, we explore its role in predicting response to immune checkpoint inhibitors and the potential of biomarkers to select which patients with cancer could ultimately benefit from TGFβ inhibition. Transforming growth factor-β (TGFβ) has a well-established role in malignancy and its inhibition has demonstrated strong preclinical activity. However, TGFβ blockade has repeatedly failed in clinical trials. Here, Barcellos-Hoff and Yom utilize human papillomavirus (HPV)-driven cancer as a model to explain these discrepancies and emphasize the need for refined strategies and understanding of TGFβ signalling to enhance therapeutic efficacy.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 7","pages":"534-544"},"PeriodicalIF":66.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087859","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

Gender and sex interactions are intrinsic components of cancer phenotypes 性别和性别互动是癌症表型的内在组成部分

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-05-19 DOI: 10.1038/s41568-025-00829-4

Joshua B. Rubin

{"title":"Gender and sex interactions are intrinsic components of cancer phenotypes","authors":"Joshua B. Rubin","doi":"10.1038/s41568-025-00829-4","DOIUrl":"10.1038/s41568-025-00829-4","url":null,"abstract":"Sex is a significant determinant of cancer incidence and outcome. The effects of sexual differentiation on normal and cancer biology underly this epidemiology. The resultant sex differences in therapeutic target pathways and processes provide a foundation for developing more personalized cancer treatments. However, our efforts at personalization cannot stop there. Humans also have gender, and sex and gender are highly interactive in individuation. Thus, we will also need to consider how gender–sex interactions (GSI) affect cancer biology and clinical parameters such as the timing of diagnoses, clinical trial enrolment, and the completeness of efficacy and toxicity data. Ignoring the effects of GSI can compromise the quality of basic biological and clinical data and the conclusions drawn from them. This is not to say that GSI will always have a significant effect or any effect at all in every cancer study. Rather, it is to say that we know enough about GSI and human cancer to anticipate measurable differences when GSI are considered in research, enabling us to experimentally determine whether their effects are significant. Here, I delve deeply into GSI and cancer, as this approach to treatment personalization holds great promise to benefit all patients with cancer. In this Perspective, Joshua Rubin emphasizes the importance of gender–sex interaction (GSI) differences in cancer biology and clinical parameters to enhance precision medicine. He outlines the challenges and opportunities of integrating GSI effects into personalized oncology and argues that optimal outcomes require extending our current molecular approaches to include family history, life history and individual vulnerabilities in our diverse groups of patients with cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 8","pages":"634-648"},"PeriodicalIF":66.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096865","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

Recent advances in therapeutic cancer vaccines 治疗性癌症疫苗的最新进展

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-05-16 DOI: 10.1038/s41568-025-00820-z

Neeha Zaidi, Elizabeth M. Jaffee, Mark Yarchoan

{"title":"Recent advances in therapeutic cancer vaccines","authors":"Neeha Zaidi, Elizabeth M. Jaffee, Mark Yarchoan","doi":"10.1038/s41568-025-00820-z","DOIUrl":"10.1038/s41568-025-00820-z","url":null,"abstract":"The success of cancer prevention vaccines targeting cancer-causing viruses has drastically reduced cancer mortality worldwide. However, the development of therapeutic cancer vaccines, which aim to elicit an immune response directly against cancer cells, has faced notable clinical setbacks. In this Review, we explore lessons learned from past cancer vaccine trials and how the field has progressed into an era of renewed promise. Previous vaccines primarily targeted tumour-associated antigens and were mainly tested as monotherapies in late-stage cancers. In contrast, contemporary vaccines focus on targeting tumour-specific antigens (neoantigens) and are showing initial evidence of clinical efficacy, particularly in early-stage cancers and precancers when combined with immune checkpoint inhibitors. Advances in tumour profiling and novel vaccine platforms have enhanced vaccine specificity and potency. We discuss recent clinical trials of therapeutic cancer vaccines and outline future directions for the field. Cancer prevention vaccines have reduced cancer-related mortalities, yet therapeutic cancer vaccine development and clinical translation continues to face challenges. Here, Zaidi, Jaffee and Yarchoan summarize the failures of cancer vaccines of the past, to highlight recent advancements in the field.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 7","pages":"517-533"},"PeriodicalIF":66.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066158","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

Reply to ‘Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies’ 回复“TP53突变的异质性需要区分p53拯救疗法”

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-05-16 DOI: 10.1038/s41568-025-00825-8

Sylvain Peuget, Galina Selivanova

引用次数: 0

Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies TP53突变的异质性需要区分p53拯救疗法

IF 66.8 1区医学

Nature Reviews Cancer Pub Date : 2025-05-16 DOI: 10.1038/s41568-025-00826-7

Jiaqi Wu, Huaxin Song, Shujun Xiao, Min Lu

引用次数: 0

Ageing lipids map melanoma’s journey 老化的脂质描绘了黑色素瘤的历程