Cancer research communications最新文献

{"title":"Impact of Staging, Histologic Grading, and Racial Background on Lip Cancer Survival in the United States: Insights from the SEER Database (2010-2020).","authors":"Muhammad Taqi, Syed Jaffar Abbas Zaidi","doi":"10.1158/2767-9764.CRC-25-0075","DOIUrl":"10.1158/2767-9764.CRC-25-0075","url":null,"abstract":"<p><p>Lip cancer has a distinct biological behavior within head and neck oncology, although population-based survival studies remain scarce. We analyzed data from the United States Surveillance, Epidemiology, and End Results (SEER) program to assess the prognostic value of tumor stage, histologic grade, and race in lip cancer diagnosed during 2010 to 2020. A retrospective cohort of 6,717 invasive lip tumors was extracted from 17 SEER registries. Cause-specific survival was estimated using Kaplan-Meier curves and compared with log-rank tests. Cox proportional hazards regression generated HRs with 95% confidence intervals. Among 4,273 lip cancer cases with SEER staging, survival varied significantly by disease extent. Localized tumors had a 94% lower risk of cancer-specific death compared with distant/regional metastasis, with median survival times of 97 and 18 months, respectively. Histologic grade correlated with survival in univariate but not multivariate analysis (after adjusting for stage and race). White and Asian/Pacific Islander patients had better survival, whereas American Indian/Alaska Native patients (0.4% of the cohort) showed a significantly elevated risk, warranting further study in this underrepresented group. In this national cohort, disease stage at diagnosis and race were key survival determinants in lip cancer. Localized tumors reduced mortality by 94% versus distant disease. Histologic grade added no further prognostic value after accounting for stage and race, underscoring the need for longer follow-up and better registry data.</p><p><strong>Significance: </strong>This SEER-based study provides the first lip-specific survival curves, revealing localized disease reduces mortality by 94% versus distant metastasis. Race (American Indian/Alaska Native patients faced triple the mortality risk) outweighed histologic grade in prognosis. Limited tumor-node-metastasis data highlighted registry gaps, whereas nodal sampling trends supported early regional assessment. Findings refine risk stratification, expose disparities needing targeted interventions, and set benchmarks for future research in this uncommon but clinically significant cancer.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1490-1500"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Activity of Datopotamab Deruxtecan (Dato-DXd), an Antibody-Drug Conjugate Targeting TROP2, in Poorly Differentiated Endometrial Carcinomas.","authors":"Niccolò G Santin, Namrata Sethi, Stefania Bellone, Cem Demirkiran, Victoria M Ettorre, Michelle Greenman, Blair McNamara, Natalia Buza, Tobias M P Hartwich, Luca Palmieri, Domenica Lorusso, Alessandro D Santin","doi":"10.1158/2767-9764.CRC-25-0251","DOIUrl":"10.1158/2767-9764.CRC-25-0251","url":null,"abstract":"<p><p>Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) targeting trophoblast antigen-2 (TROP2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver DXd, a potent topoisomerase I inhibitor. We evaluated TROP2 expression in primary endometrial cancer cell lines and the activity of Dato-DXd against endometrial cancer cell lines with different TROP2 expression in vitro and in vivo. TROP2 expression was assessed in nine primary tumor cell lines by flow cytometry. Cell viability after exposure to Dato-DXd was evaluated using flow cytometry-based assays to calculate the IC50. Bystander effect assay assessed the viability of TROP2-negative cells when cocultured with high TROP2-expressing cells. Fluorescent anti-phosphorylated histone H2AX antibody was used to demonstrate double-strand DNA breaks. Antibody-dependent cell cytotoxicity was tested in vitro using 4-hour chromium release assays. In vivo activity of Dato-DXd was evaluated against TROP2-positive endometrial cancer xenografts. A total of 78% (seven of nine) of the primary endometrial cancer cell lines expressed TROP2. Endometrial cancer cell lines expressing TROP2 were significantly more sensitive to Dato-DXd compared with control ADC. Dato-DXd-exposed, TROP2-positive endometrial cancer demonstrated increased double-strand DNA breaks compared with non-binding conjugate exposure. Dato-DXd mediated antibody-dependent cell cytotoxicity against TROP2-positive cell lines and induced significant bystander killing of TROP2-negative tumors when admixed with TROP2-positive tumors. In vivo, injection of Dato-DXd was well tolerated and demonstrated impressive tumor growth inhibition against chemotherapy-resistant poorly differentiated endometrial cancer xenografts (P < 0.0001). In conclusion, Dato-DXd is a novel ADC with remarkable preclinical activity against poorly differentiated endometrial cancer cell lines overexpressing TROP2. Clinical trials with Dato-DXd in patients with recurrent endometrial cancer are warranted.</p><p><strong>Significance: </strong>Targeted treatment of aggressive forms of endometrial cancer using the biomarker TROP2 is a significant opportunity for the development of treatments when patients are resistant to other lines of treatment. Here, we present data showing preclinical evidence of effectiveness of this biomarker-targeted therapy in endometrial cancer.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1611-1620"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12423748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGFβ inhibition during radiation therapy enhances immune cell infiltration and decreases metastases in Ewing sarcoma.","authors":"Jessica D Daley, Elina Mukherjee, David Ferraro, A Carolina Tufino, Nathanael Bailey, Shanthi Bhaskar, Nivitha Periyapatna, Ian MacFawn, Sean Hartwick, Sheryl Kunning, Cynthia Hinck, Tullia C Bruno, Adam C Olson, Linda M McAllister-Lucas, Andrew P Hinck, Kristine Cooper, Riyue Bao, Anthony R Cillo, Kelly M Bailey","doi":"10.1158/2767-9764.CRC-24-0346","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0346","url":null,"abstract":"<p><p>Ewing sarcoma (EwS) is an aggressive cancer diagnosed in adolescents and young adults. Inhibition of TGFβ is being tested in limited clinical trials for relapsed EwS. TGFβ is an immunosuppressive cytokine that exists in latent and active states. The functional impact of TGFβ inhibition on the Ewing tumor microenvironment (TME) and on Ewing tumor behavior remains largely unknown. Here, we use single-cell RNAseq analysis of human Ewing tumors to demonstrate that immune cells are the largest contributors of TGFB1 expression in the human Ewing TME. We utilize a humanized mouse model of EwS to demonstrate that TME signatures in these models differ significantly from EwS tumors developed in immunodeficient mice. Using this humanized model, we investigate the effect of TGFβ inhibition on the EwS TME during radiation therapy, a treatment that is commonly used to treat unresectable, metastatic, and relapsed/refractory EwS that is known to enhance TGFβ activation in multiple cancers. Utilizing a trivalent ligand TGFβ trap to inhibit TGF, we demonstrate that in combination with radiation therapy, TGFβ inhibition both increases EwS immune cell infiltration and decreases lung metastatic burden in vivo. These data demonstrate the value of immunocompetent models to address immune-biologic preclinical questions in EwS and demonstrate that TGFβ inhibition during radiation therapy is a promising strategy to enhance anti-tumor immune response and improve treatment efficacy for metastatic EwS.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen XVII Promotes Pancreatic Ductal Adenocarcinoma Tumor Growth through Regulation of PIK3R5.","authors":"Thomas Hank, Annie Li, Louisa Bolm, Marta Sandini, Taisuke Baba, Natalie Petruch, Julia Strässer, Kenzui Taniue, Jon M Harrison, Mari Mino-Kenudson, David T Ting, Keith D Lillemoe, Andrew L Warshaw, Carlos Fernández-Del Castillo, Kim C Honselmann, Andrew S Liss","doi":"10.1158/2767-9764.CRC-24-0392","DOIUrl":"10.1158/2767-9764.CRC-24-0392","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly chemoresistant malignancy with a dismal 11% 5-year survival rate. PDAC tumors are composed of a dense desmoplastic stroma, and the interaction of this collagen-rich tumor microenvironment with PDAC cells promotes their aggressive growth and metastatic spread. In this study, we investigated the role of collagen XVII, a unique transmembrane collagen that connects the extracellular matrix to cytoplasmic signaling complexes. Examination of PDAC tumors revealed that its expression is an independent prognostic biomarker associated with worsened oncological outcomes. Xenograft tumor studies and in vitro coculture experiments with PDAC cell lines and immortalized cancer-associated fibroblasts defined a critical role for the tumor microenvironment in mediating the expression of collagen XVII in the cancer compartment of PDAC tumors. Genetic depletion of collagen XVII reduces the viability and migration of PDAC cells in vitro and orthotopic tumor formation in vivo, underscoring its critical role in PDAC tumor biology. Tumors formed by collagen XVII-depleted PDAC cells exhibit a dramatic downregulation of phosphoinositide 3-kinase regulatory subunit 5, a regulatory subunit of the class I phosphatidylinositol 3-kinase (PI3K) γ complex, and decreased levels of downstream activated AKT. Taken together, these findings reveal collagen XVII signaling as a novel target for PDAC treatment and provide insight into the mechanisms by which it regulates PI3K activity.</p><p><strong>Significance: </strong>Our study highlights the importance of cross-talk between the tumor microenvironment and PDAC cells in mediating the expression of a key signaling pathway responsible for PI3K activity in PDAC cells.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1319-1331"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSA Secretion from Single Circulating Tumor Cells of Metastatic Castration-Naïve Prostate Cancer Patients.","authors":"Eshwari Dathathri, Fikri Abali, Michiel Stevens, Richell Booijink, Tanja C van Dijk, Khrystany T Isebia, John W M Martens, Jaco Kraan, Nick Beije, Martijn P Lolkema, Peter A W Te Boekhorst, Paul Hamberg, Brigitte C M Haberkorn, Danny Houtsma, Joan van den Bosch, Wendy M van der Deure, Ruchi Bansal, Leon W M M Terstappen","doi":"10.1158/2767-9764.CRC-25-0158","DOIUrl":"10.1158/2767-9764.CRC-25-0158","url":null,"abstract":"<p><p>PSA is the most common biomarker used in the screening and monitoring of prostate cancer. However, changes in PSA do not always reflect disease dynamics in every patient, and antihormonal agents may modulate its levels without significant antitumor effects. Changes in circulating tumor cells (CTC) have been described as a more objective measure of treatment response. Differences between PSA and CTC may be explained by heterogeneity in tumor cells producing PSA. To explore this, we measured the PSA secretion from a single CTC to gain insights into the PSA secretion heterogeneity between tumor cells. CTCs were enriched using EpCAM-based immunomagnetic enrichment in diagnostic leukapheresis of 18 patients with metastatic castration-naïve prostate cancer (mCNPC) not pretreated with any therapy, including androgen deprivation therapy. Calcein+ CD45- cells were sorted by flow cytometry and deposited as single cells on a nanowell array to measure the PSA secretion after 24 hours. In nine of 18 patients, PSA secretion was detectable and observed from both prostate-specific membrane antigen-positive and prostate-specific membrane antigen-negative CTCs. In these patients, 29% to 100% (mean, 52; median, 47) of CTCs secreted PSA, with average PSA secretion levels ranging from 4 to 11.68 pg/cell (mean, 6.38 ± 2.29; median, 6.05). Notably, a strong heterogeneity in PSA secretion was observed within each patient. Our study demonstrates that CTC in mCNPC, even before therapy, produces varying amounts of PSA and often no PSA. These findings may explain the shortcomings of PSA as a biomarker for therapy response.</p><p><strong>Significance: </strong>This study reveals heterogeneity in PSA secretion among individual CTCs from patients with mCNPC prior to any therapeutic intervention, thereby highlighting the limitations of PSA as a biomarker.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1359-1371"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Carbon Metabolism Inhibition Depletes Purines and Results in Profound and Prolonged Ewing Sarcoma Growth Suppression.","authors":"Sara Zirpoli, Noah Copperman, Shrey Patel, Alexander Forrest, Zhanjun Hou, Larry H Matherly, David M Loeb, Antonio Di Cristofano","doi":"10.1158/2767-9764.CRC-25-0218","DOIUrl":"10.1158/2767-9764.CRC-25-0218","url":null,"abstract":"<p><p>Ewing sarcoma is the second most common primary bone malignancy in adolescents and young adults. Patients who present with localized disease have experienced a steadily improving survival rate over the years, whereas those who present with metastatic disease have the same dismal prognosis as 30 years ago, with long-term survival rates of less than 20%, despite maximal intensification of chemotherapy. Thus, novel treatment approaches are a significant unmet clinical need. Targeting metabolic differences between Ewing sarcoma and normal cells offers a promising approach to improve outcomes for these patients. One-carbon metabolism utilizes serine and folate to generate glycine and tetrahydrofolate-bound one-carbon units required for de novo nucleotide biosynthesis. Elevated expression of several one-carbon metabolism genes is significantly associated with reduced survival in patients with Ewing sarcoma. We show that both genetic inhibition and pharmacologic inhibition of a key enzyme of the mitochondrial arm of the one-carbon metabolic pathway, serine hydroxymethyltransferase 2, lead to substantial inhibition of Ewing sarcoma cell proliferation and colony-forming ability and that this effect is primarily caused by depletion of glycine and one-carbon units required for the synthesis of purine nucleotides. Inhibition of one-carbon metabolism at a different node, using the clinically relevant dihydrofolate reductase inhibitor pralatrexate, similarly yields profound growth inhibition, with depletion of thymidylate and purine nucleotides. Genetic depletion of serine hydroxymethyltransferase 2 dramatically impairs tumor growth in a xenograft model of Ewing sarcoma. Together, these data establish dependence on one-carbon metabolism as a novel and targetable vulnerability of Ewing sarcoma cells, which can be exploited for therapy.</p><p><strong>Significance: </strong>Using both genetic and pharmacologic approaches, this study identifies Ewing sarcoma's dependence on one-carbon metabolism as a targetable vulnerability that can be effectively harnessed for therapy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1298-1309"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomic Analysis Reveals Complement System Changes in Irradiated Female BALB/c Mice during Mammary Carcinogenesis.","authors":"Tina Akbarzadeh, Lin Ma, Jingyun Lee, Jade Moore, William Chou, Siyavash Shabani, Cristina M Furdui, Bahram Parvin, Mary Helen Barcellos-Hoff","doi":"10.1158/2767-9764.CRC-25-0183","DOIUrl":"10.1158/2767-9764.CRC-25-0183","url":null,"abstract":"<p><p>The risk of breast cancer increases decades after ionizing radiation exposure, thereby linking aging intrinsically to the evolution of cancer. We hypothesized that radiation accelerates aging and carcinogenesis through similar pathways, specifically low-grade systemic inflammation. In this study, we used the radiation-genetic mammary chimera model to examine the differential expression of 532 plasma proteins in BALB/c female mice between radiation exposure and experiment termination at 18 months. Mice were sham irradiated or irradiated with 50 cGy prior to being orthotopically transplanted with syngeneic Trp53-null mammary epithelium and half were treated for 6 months with anti-inflammatory low-dose aspirin. Plasma was collected at 4, 8, and 18 months from non-tumor-bearing mice and from those that had developed tumors between 12 and 18 months. Plasma quantitative proteomic analysis identified significant alterations in proteins involved in the inflammatory response in irradiated mice as a function of age. Levels of C4b-binding protein were decreased at 4 months in irradiated mice compared with controls, which was blocked in aspirin-treated irradiated mice. Notable differences in the expression of proteins associated with the inflammation were evident in tumor-bearing versus similarly aged mice. Complement components C1qA, C1qB, and C1qC were significantly increased in tumor-bearing mice that had been irradiated, whereas similarly aged mice without tumors displayed a decline in complement system activity. The specific changes in the complement system, which mediates adaptive immune function, following radiation exposure may contribute to cancer progression as a function of age.</p><p><strong>Significance: </strong>Women treated with radiotherapy as children or young adults bear an increased breast cancer risk, which is more likely to be aggressive, hormone receptor negative, and immune poor. Understanding radiation effects that could be modified after exposure may lead to prevention strategies. Consistent with our hypothesis that systemic inflammation contributes to risk, the plasma proteome from mice undergoing mammary carcinogenesis demonstrates changes in the complement system.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1409-1418"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic Control and Prostate Cancer Mortality Risk in Veterans with Type 2 Diabetes Mellitus.","authors":"Kinfe G Bishu, Andrew D Schreiner, Nicholas Shungu, Vanessa A Diaz, Macelyn Batten, Mulugeta Gebregziabher","doi":"10.1158/2767-9764.CRC-25-0037","DOIUrl":"10.1158/2767-9764.CRC-25-0037","url":null,"abstract":"<p><p>This retrospective cohort study of veterans diagnosed with diabetes mellitus evaluated the association between time-varying measures of glycemic control and the time to prostate cancer-specific mortality. Competing risk Cox regression models were developed to estimate the association of glycemic control and prostate cancer mortality for the entire sample and stratified by racial and ethnic groups. A total of 763,424 veterans with type 2 diabetes mellitus (T2DM) were included. In the fully adjusted models, moderate glycemic control [hemoglobin A1c (HbA1c) 7%-8%] was associated with a 23% (HR, 0.77; 95% confidence interval, 0.68-0.85) lower risk and poor glycemic control (HbA1c >8%) was associated with a 15% (HR, 0.85; 95% confidence interval, 0.71-0.99) lower risk of prostate cancer mortality compared with good glycemic control (HbA1c <7%), respectively. In the analyses stratified by race and ethnicity, moderate glycemic control was associated with a lower risk of prostate cancer mortality in non-Hispanic White and non-Hispanic Black veterans.</p><p><strong>Significance: </strong>Unlike many other cancers, there is an inverse association between prostate cancer risk and T2DM diagnosis. In this large, retrospective study of male veterans with T2DM, we observed an inverse association between glycemic control and prostate cancer mortality. Further research is required to verify this relationship in prospective studies and identify the potential mechanisms contributing to these findings.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1256-1265"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Ferroptosis as a Biomarker to Predict Treatment Outcomes of Cancer Immunotherapy.","authors":"Zhijun Zhou, Yang Cai, Hao Yuan, Qun Chen, Sophia W Zhao, Jingxuan Yang, Mingyang Liu, Alex X Arreola, Yu Ren, Chao Xu, Lacey R McNally, Michael S Bronze, Courtney W Houchen, Kuirong Jiang, Wei R Chen, Yuqing Zhang, Min Li","doi":"10.1158/2767-9764.CRC-25-0268","DOIUrl":"10.1158/2767-9764.CRC-25-0268","url":null,"abstract":"<p><p>Immunotherapy has revolutionized the treatment paradigms of several cancer types, yet only a subset of patients derives durable clinical benefit. Ferroptosis is a programmed cell death facilitated by iron-driven overload of lipid peroxidation. We aimed to evaluate ferroptosis activity based on tumor transcriptomic profiles to determine its predictive value for immunotherapy outcomes. We analyzed RNA sequencing data from eight independent cohorts of patients with urothelial, gastric, skin, and lung cancers treated with immune checkpoint inhibitors or adoptive T-cell therapy. A ferroptosis activity model was constructed using downstream gene expression signatures. Associations with overall survival and progression-free survival were assessed. Potential mechanisms were explored by examining immunosenescence, the IFN-γ immune response pathway, and immunogenic cell death. Ferroptosis-high tumors were associated with significantly improved overall survival and progression-free survival across multiple cancer types. Integrating ferroptosis scores with tumor mutation burden, liver metastasis status, and immune microenvironment phenotypes (inflamed, excluded, desert) enhanced patient stratification and predictive accuracy. Mechanistically, ferroptosis enhanced the immune response by promoting immunogenic cell death and attenuating immunosenescence. In conclusion, elevated ferroptosis activity correlates with improved immunotherapy outcomes, potentially through increased tumor immunogenicity and reduced immunosenescence. Ferroptosis-based biomarkers may aid in identifying patients more likely to benefit from immunotherapy.</p><p><strong>Significance: </strong>Ferroptosis, an iron-dependent cell death process, is linked to improved immunotherapy outcomes. In this real-world study across eight cohorts, ferroptosis-high tumors showed 2 to 3 times longer survival. Mechanistically, ferroptosis enhanced immunogenicity and suppressed immunosenescence, highlighting its potential as a biomarker and therapeutic target to boost immunotherapy efficacy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1288-1297"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Depletion of Cancer Cells with Extrachromosomal DNA via Lentiviral Infection.","authors":"Eunhee Yi, Amit D Gujar, Dacheng Zhao, Kentaro Suina, Xue Jin, Katharina Pardon, Qinghao Yu, Larisa Kagermazova, Emmanuel E Korsah, Noah A Dusseau, Jef D Boeke, Anton G Henssen, Roel G W Verhaak","doi":"10.1158/2767-9764.CRC-25-0144","DOIUrl":"10.1158/2767-9764.CRC-25-0144","url":null,"abstract":"<p><p>Extrachromosomal DNA (ecDNA), a major focal oncogene amplification mode found across cancer, has recently regained attention as an emerging cancer hallmark, with a pervasive presence across cancers. With technical advancements such as high-coverage sequencing and live-cell genome imaging, we can now investigate the behaviors and functions of ecDNA. However, we still lack an understanding of how to eliminate ecDNA. We observed depletion of cells containing ecDNA during lentiviral but not transposon-based transduction, whereas we sought to investigate the mechanism of ecDNA behavior. This discovery may provide critical information on utilizing a lentiviral system in emerging ecDNA research. Additionally, this observation suggests specific sensitivities for cells with ecDNA.</p><p><strong>Significance: </strong>ecDNA is an essential factor in cancer progression. We found that a group of cancer cells with ecDNA is selectively depleted after lentiviral infection. This finding provides promise for ecDNA-specific targeting, suggests the need for caution in using lentivirus, and offers alternative ways to study ecDNA.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1458-1465"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}