JNCI Journal of the National Cancer Institute最新文献

{"title":"Response to Yuan and Yu.","authors":"Ioannis Zerdes, Antonios Valachis","doi":"10.1093/jnci/djaf080","DOIUrl":"https://doi.org/10.1093/jnci/djaf080","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730051","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}

{"title":"Dynamic ctDNA informs whole-course postoperative precise management of NSCLC (LUNGCA study).","authors":"Liang Xia, Qiang Pu, Ran Kang, Jiandong Mei, Lu Li, Ying Yang, Senyi Deng, Gang Feng, Yulan Deng, Fanyi Gan, Yidan Lin, Lin Ma, Feng Lin, Yong Yuan, Yang Hu, Chenglin Guo, Hu Liao, Chengwu Liu, Yunke Zhu, Wenping Wang, Zheng Liu, Yuyang Xu, Kaidi Li, Chuan Li, Weizhi Chen, Qingyun Li, Bo Du, Xiaolong Zhang, Yingli Kou, Yun Wang, Zhu Wu, Guowei Che, Yaohui Chen, Shensi Shen, Longqi Chen, Dan Xie, Lunxu Liu","doi":"10.1093/jnci/djaf061","DOIUrl":"https://doi.org/10.1093/jnci/djaf061","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor DNA (ctDNA) is valuable for detecting minimal residual disease (MRD). However, studies involving long-term blood sampling are required to comprehensively interpret the clinical use of ctDNA analyses.</p><p><strong>Methods: </strong>We conducted a prospective multicenter cohort study (LUNGCA) for dynamic ctDNA monitoring in lung cancer patients receiving curative-intent surgery. ctDNA analysis was conducted on preoperative plasma samples, at postoperative three days and one month, and then every three-six months for up to three years.</p><p><strong>Results: </strong>233 non-small cell lung cancer (NSCLC) patients and 2336 longitudinal plasma samples were included; the median follow-up was 51.4 months. Post-comprehensive treatment (after radical surgery + necessary adjuvant therapy) MRD status was better at predicting relapse than postoperative MRD status (positive predictive value: 100% vs 90.0%; negative predictive value: 90.3% vs 90.1%). Patients with positive pre-adjuvant ctDNA and targetable mutations in tumor tissues had improved recurrence-free survival (RFS) with corresponding adjuvant TKI treatment [hazard ratio (HR) = 0.01, P = .005], but adjuvant chemotherapy failed to improve RFS (HR = 0.6, P = .491). Of patients receiving adjuvant therapies, patients with a negative- or positive-negative ctDNA change pattern had favourable and similar RFS (P = .419), whereas patients with a positive- or negative-positive pattern had worse RFS (P < .001). TKI therapy was more effective than chemotherapy in clearing ctDNA. Post-relapse ctDNA negativity was associated with favorable OS (HR = 0.4; P = .029).</p><p><strong>Conclusions: </strong>Comprehensive interpretation of dynamic ctDNA monitoring data can inform precise whole-course postsurgical management of NSCLC patients.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709857","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}

{"title":"In the time of COVID-19: challenges, successes and lessons learned from studies in cancer patients.","authors":"Philip C Mack, James M Crawford, Andres Chang, Anna Yin, Sabra L Klein, Patrick Shea, Fred R Hirsch, David Zidar, Viviana Simon, Charles Gleason, Russell McBride, Carlos Cordon-Cardo, Jennifer VanOudenhove, Stephanie Halene, F Eun-Hyung Lee, Nicholas Mantis, Lawrence H Kushi, Daniela Weiskopf, Akil Merchant, Karen L Reckamp, Jacek Skarbinski, Jane C Figueiredo","doi":"10.1093/jnci/djaf073","DOIUrl":"https://doi.org/10.1093/jnci/djaf073","url":null,"abstract":"<p><p>The COVID-19 pandemic created the urgent need to monitor risk of SARS-CoV-2 infection and mortality, and to evaluate immune responses to novel vaccines. A foremost concern was the unknown risks to patients with cancer, considering their overall health, immune status and interactions with cancer therapies. The U.S. National Cancer Institute, in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to identify and establish standardized serology tests to study immune responses against SARS-CoV-2. SeroNet-sponsored institutions established cohort studies in 2020 and 2021 across the nation to prospectively follow over 3,000 patients with solid and hematologic malignancies. Concerted efforts were launched to define common data elements for self-reported and clinicopathological data as well as standardized approaches for serological, cellular and molecular assays. However, the urgency of the situation, the pace of scientific evolution and the changing public health landscape presented unique challenges to this effort. Here, we discuss these challenges, including regulatory and institution-specific requirements, enrollment of participants, data and biospecimen collection and harmonization, and the need to adapt study designs to align with the ever-changing landscape. This information is critical to the continuance of research on SARS-CoV-2 and provides a roadmap for combatting the emergence of future pathogens with pandemic potential.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700491","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}

{"title":"Association of opioid and benzodiazepine coprescribing with adverse events among older adults with cancer.","authors":"Devon K Check, Samir Soneji, Harvey Jay Cohen, Andrea Des Marais, Katie F Jones, Charles E Gaber, Jessica S Merlin, Amy O'Regan, Nicole Fergestrom, Lauren E Wilson, Aaron N Winn","doi":"10.1093/jnci/djaf072","DOIUrl":"https://doi.org/10.1093/jnci/djaf072","url":null,"abstract":"<p><strong>Background: </strong>Many older adults with cancer are coprescribed opioids/benzodiazepines; evidence on harms is lacking.</p><p><strong>Methods: </strong>Using SEER-Medicare (2012-2019), we identified patients with breast, colorectal, or lung cancer. Cox proportional hazards models estimated the adjusted hazard ratios (HR) of coprescribing (measured from claims, at the day level) with the immediate risk of overdose, fall/fracture, and all-cause hospitalization. In a secondary analysis, models were stratified by ≥ 90 days of continuous medication supply.</p><p><strong>Results: </strong>In our cohort of 107,288 patients, compared to those prescribed neither medication, those prescribed benzodiazepines had an increase in the immediate risk of falls/fractures (HR: 1.17, 95% CI: 1.02-1.34) and all-cause hospitalizations (HR: 1.08, 95% CI: 1.04-1.12). Patients prescribed opioids had an increase in the immediate risk of overdose (HR: 5.62, 95% CI: 4.86, 5.62), falls/fractures (HR: 1.56, 95% CI: 1.41, 1.73), and all-cause hospitalizations (HR: 1.26, 95% CI: 1.23, 1.30). HRs were similar for patients coprescribed opioids/benzodiazepines. For patients without continuous exposure to one or both medications, effects were larger for coprescribed opioids/benzodiazepines vs opioids for overdose (HR: 15.22, 95% CI: 8.79-26.35 vs HR: 6.85, 95% CI: 6.85- 26.35) and all-cause hospitalization (HR: 3.21, 95% CI: 2.60-3.96 vs HR: 1.98, 95% CI: 1.87- 2.10).</p><p><strong>Conclusions: </strong>Overall, compared to no prescribing, benzodiazepine prescribing and opioid prescribing were each associated with an increase in the immediate risk of adverse events. Effects were similar for those prescribed opioids and those coprescribed opioids/benzodiazepines. For patients with intermittent vs long-term medication exposure, coprescribing additionally increased the risk of overdose and all-cause hospitalization.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669906","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}

{"title":"Sex-specific radiation-associated lung cancer mortality risks as impacted by smoking among US radiologic technologists.","authors":"Cato M Milder, Elizabeth K Cahoon, Sara J Schonfeld, Dale L Preston, Bruce H Alexander, Martha S Linet, Cari M Kitahara","doi":"10.1093/jnci/djaf064","DOIUrl":"https://doi.org/10.1093/jnci/djaf064","url":null,"abstract":"<p><strong>Background: </strong>The Life Span Study of Japanese atomic bomb survivors estimated greater risks of radiation-associated lung cancer among females than males, with direct implications for occupational radiation safety policy. To evaluate replicability of these findings in radiation workers, we assessed sex-specific radiation-associated risks of lung cancer mortality in a large cohort of U.S. radiologic technologists.</p><p><strong>Methods: </strong>Using data from four questionnaires (1983-2013), we reconstructed lifetime smoking history for 83,715 female and 26,650 male technologists. We estimated individual lung occupational radiation doses using badge dose and questionnaire data. We used Poisson regression to investigate joint radiation-smoking effects on sex-averaged and sex-specific lung cancer mortality risk.</p><p><strong>Results: </strong>For 1243 female and 607 male technologists who died from lung cancer, median cumulative lung dose was 16.2mGy (non-cases: 7.7mGy) and 24.5mGy (non-cases: 10.1mGy), respectively. Excess risk of lung cancer increased with increasing radiation dose. However, smoking modified this effect: the radiation effect at 100mGy increased until 16 cigarettes/day, after which it declined. Excess relative risk (ERR) per 100mGy was greater among males (never smoking additive ERR = 1.98; 95%CI = 0.34, 6.25) than females (never smoking additive ERR = 0.40; 95%CI=-0.02, 1.21); sex-differences persisted up to ∼40 cigarettes/day.</p><p><strong>Conclusions: </strong>Our results indicated radiation-associated risks of lung cancer mortality were stronger in males than females, in contrast to the Life Span Study. However, both studies found radiation-associated risks were highest in workers with light-to-moderate smoking intensity. Altogether, these findings reinforce the importance of rigorous radiation protection measures for all radiation workers, regardless of sex, alongside interventions to support smoking cessation.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669909","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}

{"title":"Associations of self-identified race and ethnicity and genetic ancestry with mortality among cancer survivors.","authors":"Jacqueline B Vo, Derek W Brown, Ian D Buller, Jaimie Z Shing, Naoise Synnott, Rena R Jones, Maria Teresa Landi, Wen-Yi Huang, Mitchell J Machiela, Amy Berrington De Gonzalez, Timiya S Nolan, Peter Kraft, Faustine Williams, Neal D Freedman","doi":"10.1093/jnci/djaf066","DOIUrl":"https://doi.org/10.1093/jnci/djaf066","url":null,"abstract":"<p><p>Self-identified race and ethnicity (SIRE) and genetic ancestry (GA) are potentially associated with disparities in health outcomes; however, independent effects of SIRE and GA on mortality in cancer survivors including when adjusting for multiple risk factors are understudied. Among 23,445 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian Screening Trial, SIRE was associated with mortality among prostate, colorectal, lung, ovarian, and breast cancer survivors; GA was associated with mortality among prostate, colorectal, and breast cancer survivors. Associations were strong when adjusting for age at cancer diagnosis, sex, and tumor characteristics, but attenuated when adjusting for individual-level factors and population-level socioeconomic status. For example, mortality risk was higher among Black vs White prostate cancer survivors and African GA vs European GA, but associations were attenuated after multilevel adjustment. Results suggest SIRE and GA do not solely reflect biologic variation; rather, social factors may drive mortality differences by SIRE and GA.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669907","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}

{"title":"Effects of exercise on inflammation in female survivors of nonmetastatic breast cancer: a systematic review and meta-analysis.","authors":"Francesco Bettariga, Dennis R Taaffe, Anita Borsati, Alice Avancini, Sara Pilotto, Stefano G Lazzarini, Pedro Lopez, Luca Maestroni, Umberto Crainich, John P Campbell, Timothy D Clay, Daniel A Galvão, Robert U Newton","doi":"10.1093/jnci/djaf062","DOIUrl":"https://doi.org/10.1093/jnci/djaf062","url":null,"abstract":"<p><strong>Background: </strong>Despite advances in breast cancer treatment, recurrence remains common and contributes to higher mortality risk. Among the potential mechanisms, inflammation plays a key role in recurrence by promoting tumor progression. Exercise provides a wide array of health benefits and may reduce inflammation, potentially reducing mortality risk. However, the effects of exercise, including mode (ie, resistance training [RT], aerobic training [AT], and combined RT and AT) and program duration, on inflammatory biomarkers in breast cancer survivors remain to be elucidated.</p><p><strong>Methods: </strong>A systematic search was undertaken in PubMed, CINAHL, Embase, SPORTDiscus and CENTRAL in August 2024. Randomized controlled trials examining the effects of exercise on IL-1β, IL-6, IL-8, IL-10, TNF-α, and CRP were included. A random-effects meta-analysis was undertaken to quantify the magnitude of change.</p><p><strong>Results: </strong>Twenty-two studies were included (n = 968). Exercise induced small to large significant reductions in IL-6 (SMD = -0.85; 95% CI = -1.68 to -0.02; p = .05) and TNF-α (SMD = -0.40; 95% CI = -0.81 to 0.01; p = .05) and a trend for a decrease in CRP. When stratifying by exercise mode, trends toward reduction in IL-6 and TNF-α were observed for combined exercise, whilst changes were not generally affected by exercise program duration.</p><p><strong>Conclusion: </strong>Exercise, especially combined RT and AT, can reduce pro-inflammatory biomarkers, and may be a suitable strategy to reduce inflammation in breast cancer survivors. However, further research is needed to investigate the effects of exercise mode and program duration on markers of inflammation in this survivor group.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669908","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}

{"title":"Initial evaluation of a new cervical screening strategy combining human papillomavirus genotyping and automated visual evaluation: the Human Papillomavirus-Automated Visual Evaluation Consortium.","authors":"Brian Befano, Jayashree Kalpathy-Cramer, Didem Egemen, Federica Inturrisi, José Jeronimo, Ana Cecilia Rodríguez, Nicole Campos, Miriam Cremer, Ana Ribeiro, Kayode Olusegun Ajenifuja, Andrew Goldstein, Amna Haider, Karen Yeates, Margaret Madeleine, Teresa Norris, Jaqueline Figueroa, Karla Alfaro, Tainá Raiol, Clement Adepiti, Judith Norman, George Kassim Chilinda, Bariki Mchome, Yeycy Donastorg, Xolisili Dlamini, Gabriel Conzuelo, Adekunbiola A Banjo, Pauline Chone, Alex Mremi, Arismendi Benitez, Zeev Rosberger, Te Vantha, Ignacio Prieto-Egido, Jen Boyd-Morin, Christopher Clark, Scott Kinder, Nicolas Wentzensen, Kanan Desai, Rebecca Perkins, Silvia de Sanjosé, Mark Schiffman","doi":"10.1093/jnci/djaf054","DOIUrl":"https://doi.org/10.1093/jnci/djaf054","url":null,"abstract":"<p><p>The HPV-Automated Visual Evaluation (PAVE) Consortium is validating a cervical screening strategy enabling accurate cervical screening in resource-limited settings. A rapid, low-cost HPV assay permits sensitive HPV testing of self-collected vaginal specimens; HPV-negative women are reassured. Triage of positives combines HPV genotyping (four groups in order of cancer risk) and visual inspection assisted by automated cervical visual evaluation (AVE) that classifies cervical appearance as severe, indeterminate, or normal. Together, the combination predicts which women have precancer, permitting targeted management to those most needing treatment. We analyzed CIN3+ yield for each PAVE risk level (HPV genotype crossed by AVE classification) from nine clinical sites (Brazil, Cambodia, Dominican Republic, El Salvador, Eswatini, Honduras, Malawi, Nigeria, and Tanzania). Data from 1832 HPV-positive participants confirmed that HPV genotype and AVE classification each strongly and independently predict risk of histologic CIN3+. The combination of these low-cost tests provided excellent risk stratification, warranting pre-implementation demonstration projects.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657204","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}

{"title":"Spectrum of cancer risk in Asian American and Pacific Islander solid organ transplant recipients.","authors":"Jun Tao, Jaimie Z Shing, Kelly Yu, Aimée R Kreimer, Mei-Chin Hsieh, Karen S Pawlish, Jie Li, Baozhen Qiao, Judy R Rees, Kekoa Taparra, Jacqueline B Vo, Eric A Engels","doi":"10.1093/jnci/djaf069","DOIUrl":"https://doi.org/10.1093/jnci/djaf069","url":null,"abstract":"<p><strong>Background: </strong>Solid organ transplant recipients (SOTRs) have increased cancer risk, which may differ across racial groups. Cancer risk among Asian American and Pacific Islander SOTRs is ill-defined.</p><p><strong>Methods: </strong>We evaluated Asian, Pacific Islander, and White SOTRs from a linkage of the United States SOTR registry with 34 cancer registries (1990-2019). We calculated age-and-sex adjusted incidence rate ratios (aIRRs) to compare cancer risk between races and standardized incidence ratios (SIRs) to measure risk relative to race-matched general populations.</p><p><strong>Results: </strong>Compared with Asian SOTRs, Pacific Islander SOTRs had notably higher incidence of pancreatic cancer (aIRR = 3.7, 95%CI = 1.6-8.6) and melanoma (aIRR = 6.7, 95%CI = 1.2-36). Compared with White SOTRs, Asian and Pacific Islander SOTRs had lower melanoma incidence but higher nasopharyngeal carcinoma incidence. Compared with the general population, Asian SOTRs had increased risk of cancers of the anus (SIR = 7.9, 95%CI = 3.6-15), penis (SIR = 8.9, 95%CI = 2.9-21), non-epithelial skin (SIR = 9.8, 95%CI = 5.4-17), kidney (SIR = 5.3, 95%CI = 4.3-6.5), and renal pelvis (SIR = 7.4, 95%CI = 3.7-13); non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) (SIR = 6.4, 95%CI = 5.6-7.3); Hodgkin lymphoma (SIR = 6.1, 95%CI = 2.8-12); and Kaposi sarcoma (SIR = 15, 95%CI = 6.6-30). Compared with the general population, Pacific Islander SOTRs had increased risk of cancers of the anus (SIR:12, 95%CI = 1.5-45), pancreas (SIR = 3.3, 95%CI = 1.3-6.8), non-epithelial skin (SIR = 9.3, 95%CI = 1.1, 34), and thyroid (SIR = 3.4, 95%CI = 1.2-7.4); NHL/CLL (SIR = 4.5, 95%CI = 2.3-7.9); and Kaposi sarcoma (SIR = 71, 95%CI = 8.6-258).</p><p><strong>Conclusions: </strong>Asian, Pacific Islander and White SOTRs all experienced elevated cancer risk compared with their race-matched general population. Different cancer risks in these racial groups might be explained by differences in risk factors in the general population or unique features of SOTRs in these groups.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669910","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}

{"title":"The NuRD-SWI/SNF antagonism regulates the coordinated activation of EMT and inflammation in oral cancer.","authors":"Roberto Stabile, Francesco A Tucci, Mathijs P Verhagen, Carmen Embregts, Thierry P P van den Bosch, Rosalie Joosten, Maria J De Herdt, Berdine van der Steen, Alex L Nigg, Senada Koljenović, Jose A Hardillo, C Peter Verrijzer, Adrian Biddle, Robert J Baatenburg de Jong, Pieter J M Leenen, Riccardo Fodde","doi":"10.1093/jnci/djaf065","DOIUrl":"https://doi.org/10.1093/jnci/djaf065","url":null,"abstract":"<p><p>Phenotypic plasticity and inflammation, two well-established hallmarks of cancer, play key roles in local invasion and distant metastasis by enabling the rapid adaptation of tumor cells to dynamic micro-environmental changes. Here, we show that in oral squamous carcinoma cell carcinoma (OSCC), the competition between the NuRD and SWI/SNF chromatin remodeling complexes plays a pivotal role in regulating both epithelial-mesenchymal plasticity (EMP) and inflammation. By perturbing these complexes, we demonstrated their opposing downstream effects on the inflammatory pathways and EMP regulation. In particular, downregulation of the BRG1-specific SWI/SNF complex deregulates key inflammatory genes, such as TNF-α and IL6, in opposite ways when compared with the loss of CDK2AP1, a key member of the NuRD complex. We showed that CDK2AP1 genetic ablation triggers a pro-inflammatory secretome encompassing several chemokines and cytokines, thus promoting the recruitment of monocytes into the tumor microenvironment (TME). Furthermore, CDK2AP1 deletion stimulates their differentiation into M2-like macrophages, as validated on tumor microarrays from OSCC patient-derived tumor samples. Further analysis of the inverse correlation between CDK2AP1 expression and TME immune infiltration revealed specific downstream effects on the abundance and localization of CD68+ macrophages. Our study sheds light on the role of chromatin remodeling complexes in OSCC locoregional invasion and highlights the potential of CDK2AP1 and other members of NuRD and SWI/SNF chromatin remodeling complexes as prognostic markers and therapeutic targets.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669911","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}