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Cancer Drugs and United States Tariffs: Attention Must Be Paid. 抗癌药物和美国关税：必须引起注意。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-09-01 Epub Date: 2025-09-25 DOI: 10.1097/PPO.0000000000000785
Maxwell L Izen, June M McKoy, Linda Martin, Chadi Nabhan, Gretchen LeFever Watson, Joseph Magagnoli, Kenneth R Carson, Kevin Knopf, Edward Smith, Edward Zyszkowski, Mia Lynch, Demir Uslu, Peter Georgantopoulos, David Aboulafia, Charles L Bennett
{"title":"Cancer Drugs and United States Tariffs: Attention Must Be Paid.","authors":"Maxwell L Izen, June M McKoy, Linda Martin, Chadi Nabhan, Gretchen LeFever Watson, Joseph Magagnoli, Kenneth R Carson, Kevin Knopf, Edward Smith, Edward Zyszkowski, Mia Lynch, Demir Uslu, Peter Georgantopoulos, David Aboulafia, Charles L Bennett","doi":"10.1097/PPO.0000000000000785","DOIUrl":"10.1097/PPO.0000000000000785","url":null,"abstract":"<p><p>The Trump Administration has signaled its intent to impose tariffs on pharmaceuticals worldwide, raising uncertainty about the potential impact on cancer treatments in the United States. Increasing concern surrounds the possibility that these tariffs may compromise the quality of care and adversely affect the survival outcomes of cancer patients across the country. The proposed tariffs on pharmaceuticals threaten to worsen already high drug costs and disrupt access to essential cancer treatments. As Martha Basey of Patients for Affordable Drugs points out, \"We know that already one in three people in the United States can not fill their prescriptions because of high costs. We expect the pharmaceutical companies not to let this chaos over trade go to waste Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation and try to raise prices while pointing the finger at tariffs.\" Given the complex global supply chain and existing drug shortages, tariffs risk increasing prices without encouraging more domestic production or improving patient care. For these reasons, policy experts strongly caution against imposing broad tariffs on cancer medicines and advocate for alternative solutions to protect access to and affordability of these medications.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor Evolution Driving Genome Instability, Immune Interactions, and Response to Radiotherapy. 肿瘤进化驱动基因组不稳定性、免疫相互作用和对放疗的反应。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000777
George Seed, France Truong, Rahma Riahi, Ben O'Leary
{"title":"Tumor Evolution Driving Genome Instability, Immune Interactions, and Response to Radiotherapy.","authors":"George Seed, France Truong, Rahma Riahi, Ben O'Leary","doi":"10.1097/PPO.0000000000000777","DOIUrl":"10.1097/PPO.0000000000000777","url":null,"abstract":"<p><p>This review article explores the role of immuno-radiotherapy in the context of genome instability and tumor evolution. Genomic changes in tumors exist in a delicate balance with the immune system, offering evolutionary pathways to adapt and grow but risking provoking an immune response. Rapid developments across both immunotherapy and radiotherapy have raised questions about the potential benefits combination therapy, and how best to identify ideal treatment populations. Here we discuss foundational studies of genomic instability and tumor evolution, how these paradigms translate into immune surveillance and evasion, and subsequently go on to explore recent preclinical and clinical studies of both treatment modalities. Understanding how cancers evolve in the context of the immune system could provide a key insight in delivering better therapies that could overcome treatment resistance.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modulating Redox Biology to Improve Radiation Responses. 调节氧化还原生物学以改善辐射反应。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000778
Jacky K Leung, Ryan Panchal, Selvakumar Anbalagan, Emily P Durie, Jörg Mansfeld, Navita Somaiah
{"title":"Modulating Redox Biology to Improve Radiation Responses.","authors":"Jacky K Leung, Ryan Panchal, Selvakumar Anbalagan, Emily P Durie, Jörg Mansfeld, Navita Somaiah","doi":"10.1097/PPO.0000000000000778","DOIUrl":"10.1097/PPO.0000000000000778","url":null,"abstract":"<p><p>Redox biology plays an important role in cancer progression and therapy resistance. Tumor cells maintain elevated levels of reactive oxygen species to support proliferation while upregulating antioxidant defences to avoid oxidative cell death. Radiotherapy, a standard treatment for over half of all cancer patients, relies on the generation of reactive oxygen species and adequate oxygen availability for efficacy. However, hypoxic tumor microenvironments and enhanced antioxidant systems contribute significantly to radioresistance. This redox imbalance, which is characteristic of tumor cells, presents a therapeutic opportunity where modifying redox biology may sensitise tumors to radiation and promote cell death. In this review, we examine how redox signalling supports tumor survival and highlight emerging clinical strategies that target redox pathways to overcome resistance and improve radiotherapy outcomes.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Radiation-dependent Nucleic Acid Sensing, and Its Possible Impact on Radiotherapy. 辐射依赖性核酸传感及其对放射治疗的可能影响。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000775
Robert J Pickering, Christian Zierhut
{"title":"Radiation-dependent Nucleic Acid Sensing, and Its Possible Impact on Radiotherapy.","authors":"Robert J Pickering, Christian Zierhut","doi":"10.1097/PPO.0000000000000775","DOIUrl":"10.1097/PPO.0000000000000775","url":null,"abstract":"<p><p>DNA damage and chromosomal instability can promote sterile inflammatory responses in cells, similar to those induced by pathogen infection. Primary contributors to this phenomenon are cGAS-dependent and AIM2-dependent DNA-sensing mechanisms, as well as RIG-I-dependent, MDA5-dependent, and ZBP1-dependent RNA-sensing mechanisms. Work over the last decade has established that some or all of these pathways may also be activated by radiotherapy, potentially modulating the behavior of irradiated tumours. With an emphasis on tumor cells, we review here how innate immune signalling may become activated during radiotherapy, and how it may impact the behavior of irradiated cells, as well as how this might pattern the tumor microenvironment.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Modulating Purinergic Signaling to Improve Radiotherapy Outcomes. 调节嘌呤能信号以改善放疗结果。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000779
Jessica Oliver, Victor Gray, Linda S Li, Ricardo M Sainz, Erik Wennerberg
{"title":"Modulating Purinergic Signaling to Improve Radiotherapy Outcomes.","authors":"Jessica Oliver, Victor Gray, Linda S Li, Ricardo M Sainz, Erik Wennerberg","doi":"10.1097/PPO.0000000000000779","DOIUrl":"10.1097/PPO.0000000000000779","url":null,"abstract":"<p><p>Over the past decades, the immunomodulatory properties of radiotherapy have started to be uncovered. This has prompted a new way of interpreting radiotherapy responses and opened novel avenues for combining radiotherapy with immunotherapy. A key component of radiation-induced immunogenicity is the extracellular release of danger-associated molecular patterns, including ATP and NAD. The presence of these purine metabolites in the extracellular space represents a potent signal of immune alert. However, the sensing and catabolism of extracellular ATP and NAD by purinergic receptors and ectonucleotidases, respectively, are perturbed in cancer, and the characterization of their effects on antitumor immune responses is a rapidly evolving research field. However, the impact of purinergic signalling on radiation-induced immune responses remains poorly understood. Here, we review the immunostimulatory and immunosuppressive processes induced by ATP and NAD in tumours, discuss their role in cancer radiotherapy, and opportunities for targeting them to improve responses in cancer patients.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Harnessing Immunogenic Cell Death to Boost the Impact of Radiation Therapy. 利用免疫原性细胞死亡增强放射治疗的影响。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000780
Jonathan Mannion, Pascal Meier
{"title":"Harnessing Immunogenic Cell Death to Boost the Impact of Radiation Therapy.","authors":"Jonathan Mannion, Pascal Meier","doi":"10.1097/PPO.0000000000000780","DOIUrl":"10.1097/PPO.0000000000000780","url":null,"abstract":"<p><p>Harnessing radiotherapy (RT) to effectively eliminate cancer cells has been a cornerstone of clinical oncology for decades. Beyond its well-established cytotoxic effects, RT triggers a diverse array of tumor cell death modalities, including apoptosis, necrosis, mitotic catastrophe, and, under specific conditions, immunogenic forms such as necroptosis and pyroptosis. Although apoptosis serves as a homeostatic and immunologically silent process that removes over 200 billion cells daily in our body, lytic forms of regulated cell death, such as necroptosis and pyroptosis, have evolved to detect and combat pathogens, thereby acting as potent danger signals that alert and mobilise immune responses. Here, we review emerging pathogen-mimicry approaches to rewire RT-induced cell death towards more immunogenic cell death modalities, aiming to transform RT from a primarily tumor-debulking modality into a driver of durable anti-tumor immunity.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Modulating T-cell Responses to Enhance the Effects of Radiotherapy. 调节t细胞反应增强放疗效果。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000782
Matías Fernández Muñoz, Mai K Bishr, Ben O'Leary, Alan Melcher, Kevin Harrington
{"title":"Modulating T-cell Responses to Enhance the Effects of Radiotherapy.","authors":"Matías Fernández Muñoz, Mai K Bishr, Ben O'Leary, Alan Melcher, Kevin Harrington","doi":"10.1097/PPO.0000000000000782","DOIUrl":"10.1097/PPO.0000000000000782","url":null,"abstract":"<p><p>Radiotherapy has been a key component of cancer treatment for over a hundred years, with the understanding that its action was driven only by direct and indirect toxic effects on the tumor cells. With the advent of immunotherapy in recent decades, interest in radiotherapy has expanded beyond just its ability to kill malignant cells directly, to include the potential for augmenting the antitumor immune response in combination with immunotherapy. However, radiotherapy has also been clearly demonstrated to exert immunosuppressive effects, reported in both preclinical and clinical settings, and this means that it has a double-edged immune effect. The cytotoxic effects of T cells are a critical element of the antitumor immune response, and it is cytotoxic T lymphocytes (CTL) that have been the primary target of clinically mature immunotherapies to date, notably antibodies blocking negative regulation of T cells. In this context, the question is how the combination of radiotherapy and immunotherapy can be optimized to leverage the immune-promoting effects of radiotherapy, while minimizing its immune deleterious consequences. In this review, we present the most recent understanding of this promising therapeutic combination, with a specific focus on modulating T-cell responses, also highlighting the need for more in-depth investigation of the responsible underlying mechanisms of action.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Targeting Cancer-associated Fibroblasts (CAFs) to Optimize Radiation Responses. 靶向癌症相关成纤维细胞（CAFs）优化辐射反应。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000776
Katie O'Fee, Amy Burley, Sarah Stewart, Anna Wilkins
{"title":"Targeting Cancer-associated Fibroblasts (CAFs) to Optimize Radiation Responses.","authors":"Katie O'Fee, Amy Burley, Sarah Stewart, Anna Wilkins","doi":"10.1097/PPO.0000000000000776","DOIUrl":"10.1097/PPO.0000000000000776","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment with diverse functions. CAFs are heterogeneous; although their roles are primarily tumor-promoting, recent research suggests that in specific contexts, certain CAF subtypes may have tumour-restraining functions. Importantly, CAFs are capable of surviving following high doses of radiation. Here, CAFs typically undergo senescent changes, which trigger a diverse secretory phenotype. This phenotype presents a number of therapeutic opportunities for targeting CAFs to improve tumor cure rates following radiation. This review summarizes our current understanding of CAF development and heterogeneity, as well as presenting mechanisms by which CAFs are activated by radiation. Finally, recent examples demonstrate how targeting CAFs can synergize with radiation for therapeutic gain.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Alternative Radiotherapy Delivery Approaches to Modulate Radiation Response. 调节辐射反应的替代放射治疗递送方法。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000781
Joanna Wilk, Carol Box, Kevin Harrington, Simeon Nill, Uwe Oelfke
{"title":"Alternative Radiotherapy Delivery Approaches to Modulate Radiation Response.","authors":"Joanna Wilk, Carol Box, Kevin Harrington, Simeon Nill, Uwe Oelfke","doi":"10.1097/PPO.0000000000000781","DOIUrl":"10.1097/PPO.0000000000000781","url":null,"abstract":"<p><p>Spatially fractionated (SFRT) and FLASH radiotherapy (RT) are alternative means of dose delivery that are expected to widen the therapeutic window of clinical RT. The biological mechanisms for the observed effects of normal tissue-sparing with maintained tumor control probability are unknown. First, we introduce the preclinical research technologies for SFRT and FLASH-RT with photon beams, which include carbon nanotubes and modifications of standard small animal irradiators. As a novel concept, we highlight the potential importance of line-focussed x-ray tubes. Following that, we review immunological anti-tumor responses observed in various animal models for both alternative irradiation modalities. While there is agreement that SFRT and FLASH modulate the tumor immune microenvironment, at present, it is not clear if the anti-tumor immunity generated is more beneficial than that resulting from conventional RT. Further preclinical research is required to determine which aspects of the SFRT-mediated or FLASH-mediated anti-tumor immune response could be exploited for the eventual benefit of cancer patients.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Interfaces Between the DNA Damage Response and Anti-cancer Immunity. DNA损伤反应与抗癌免疫之间的界面。
IF 2.1 4区 医学
Cancer journal Pub Date : 2025-07-01 Epub Date: 2025-08-11 DOI: 10.1097/PPO.0000000000000773
Charleen Chan Wah Hak, Magnus Dillon
{"title":"Interfaces Between the DNA Damage Response and Anti-cancer Immunity.","authors":"Charleen Chan Wah Hak, Magnus Dillon","doi":"10.1097/PPO.0000000000000773","DOIUrl":"10.1097/PPO.0000000000000773","url":null,"abstract":"<p><p>The complex interplay between DNA damage (DDR) and immune responses presents therapeutic opportunities for enhancing antitumour immunity, particularly in the context of radiotherapy. We discuss how DNA damage leads to immunomodulation and how conventional DNA-damaging therapies modulate the immune response, with both immunostimulatory and immunosuppressive effects. We discuss present clinically exploited DDR-immune links, such as the use of genomic instability and DDR status as predictive biomarkers. We present strategies, such as combined DDR-radiation, which have shown promise in preclinical and early clinical studies as immunomodulatory radiosensitizing therapies.</p>","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"31 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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