Cancer Medicine最新文献

{"title":"Landscape of TET2 Mutations: From Hematological Malignancies to Solid Tumors","authors":"Zoë L. Hawking,&nbsp;James M. Allan","doi":"10.1002/cam4.70792","DOIUrl":"10.1002/cam4.70792","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The ten–eleven translocation (TET) enzyme family is a key regulator of DNA methylation, responsible for the conversion of 5-methylcytosine to 5-hydroxymethylcytosine to promote locus-specific demethylation. Thus, it is not surprising that loss or attenuation of TET enzymes is implicated in genomic hypermethylation and transcriptional reprogramming that drives cancer development. Somatic mutations in <i>TET2</i> are observed in the bone marrow of 5%–10% of healthy adults over 65 years of age, imparting a hematopoietic stem cell advantage and subsequent clonal hematopoiesis of indeterminate potential (CHIP), a condition which is associated with increased risk of myeloid malignancy. Somatic <i>TET2</i> mutations are frequently reported in myeloid disorders, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Evidence suggests that <i>TET2</i> mutations also affect prognosis in myeloid leukemia and other hematopoietic malignancies. However, there is a paucity of collated data on the frequency of <i>TET2</i> mutations in solid human cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We review the published literature on <i>TET2</i> mutation in human solid cancers and explore their frequency and impact on patient outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results &amp; Conclusions</h3>\u0000 \u0000 <p>Somatic <i>TET2</i> mutations are reported in numerous solid human cancers, including those arising in the skin, lung and prostate. Many of the somatic <i>TET2</i> mutations reported in solid cancers are recurrent, suggesting functionality. There is also evidence to suggest that somatic <i>TET2</i> mutations affect prognosis in solid human cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the Diagnosis and Survival of Early Onset Bowel Cancer Among First Nations Peoples in Queensland, Australia","authors":"Tsegaw Amare Baykeda,&nbsp;Shafkat Jahan,&nbsp;Kirsten Howard,&nbsp;Rakhee Raghunandan,&nbsp;Gail Garvey","doi":"10.1002/cam4.70821","DOIUrl":"10.1002/cam4.70821","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The incidence of early-onset bowel cancer (EOBC) is increasing in Australia and globally. However, the burden of EOBC among First Nations Australians is rarely determined. This study aimed to quantify the diagnosis and survival rates of EOBC among First Nations Peoples in Queensland, Australia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CancerCostMod, a linked administrative dataset of patients diagnosed with cancer in Queensland from 1st July 2011 to 30th June 2015, was used. EOBC was defined as a diagnosis of bowel cancer (i.e., colon, rectosigmoid, or rectal cancer) at 18–49 years of age. A multivariable logistic regression analysis was employed to determine the association of Indigenous status and other factors with a diagnosis of EOBC. Five-year survival rates were used to estimate the survival rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 11,702 bowel cancer cases, 9.2% (95% CI: 8.7%–9.7%) were EOBC, with 19% among First Nations peoples and 9% among Non-First Nations. First Nations Australians had 2.6 times the odds of EOBC diagnosis (95% CI: 1.7–4.0) compared with Non-First Nations Australians. Overall, EOBC patients showed a significantly higher 5-year survival rate of 77% compared with 60% for late-onset bowel cancer patients. However, First Nations EOBC patients showed a lower 5-year survival rate (73%) than Non-First Nations EOBC patients (77%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>First Nations Australians have more than double the diagnosis rates and lower 5-year survival for EOBC compared to Non-First Nations. Whilst the recent lowering of the age eligibility for the National Bowel Cancer Screening Program is a beneficial strategy to address the increasing incidence of EOBC, special consideration should be given to addressing the higher diagnosis rates and lower survival among First Nations Australians. This study raises the potential for further lowering the age eligibility for First Nations Australians to ensure younger First Nations Australians can access screening for earlier detection, thereby improving their survival from bowel cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ecological Analysis of HPV Vaccination in the United States Before and During the COVID-19 Pandemic by Age, Sex, and Urbanicity Using Private Insurance Claims Data","authors":"Milkie Vu,&nbsp;Jingjing Li,&nbsp;Kai Hong,&nbsp;Jennifer W. Kaminski,&nbsp;Bo-Hyun Cho,&nbsp;Yoonjae Kang","doi":"10.1002/cam4.70761","DOIUrl":"10.1002/cam4.70761","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>We aim to assess HPV vaccine administration among privately insured populations before and during the COVID-19 pandemic in the United States and stratify the assessments by demographic and geographic characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the Merative MarketScan Commercial Claims and Encounters Database, we estimated monthly and yearly HPV vaccine administration among people aged 9–26 from 2019 to 2022, measured as the proportion of the enrolled population who received ≥ 1 dose of HPV vaccine during that month or year, and their relative percent change from 2020 to 2022, compared to the same period in 2019, overall and stratified by age group, sex, and urbanicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HPV vaccine administration in 2020, 2021, and 2022 was lower than in 2019 and continued to decline for all age groups. The relative percent change in rate in 2022 relative to 2019 was −6.0% among children, −38.3% among adolescents, and −42.5% among young adults. The patterns were similar across subgroups, with certain disparities in magnitude. By subpopulations, the highest percent declines in 2022 relative to 2019 in each age group were observed among children in rural areas (−13.5%), male adolescents (−39.8%), and young adults in rural areas (−46.0%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>During the COVID-19 pandemic, HPV vaccine administration dropped substantially and had not exceeded the pre-pandemic levels by the end of 2022, with larger declines seen among male adolescents and young adults in rural areas. Our results highlight the need for continuing monitoring and targeted intervention strategies to improve HPV vaccine administration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics Identification of Lactate-Associated Genes in Hepatocellular Carcinoma: G6PD's Role in Immune Modulation","authors":"Hao-ran Qu,&nbsp;Chao-qun Wang,&nbsp;Su-juan Sun,&nbsp;Wen-wen Zhang,&nbsp;Cheng-hao Liu,&nbsp;Xuan-shuang Du,&nbsp;Yao-yi-ao Shu,&nbsp;Xi-cheng Wang,&nbsp;Qin Pan,&nbsp;Feng-ling Luo,&nbsp;Hong-yan Wu,&nbsp;Xiao-lian Zhang,&nbsp;Min Liu","doi":"10.1002/cam4.70801","DOIUrl":"10.1002/cam4.70801","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a major global health issue, with poor prognosis often associated with dysregulated metabolic pathways, especially lactate metabolism. This study explored the prognostic significance of lactate-associated genes in HCC and their potential as therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed RNA-seq and clinical data from 374 patients with HCC from The Cancer Genome Atlas (TCGA) database. Using Cox regression, LASSO analysis, and Kaplan–Meier survival curves, we identified key lactate-associated genes associated with patient outcomes. Functional validations, including Western blot, flow cytometry, and molecular docking studies, were performed to confirm the biological impact of these genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>G6PD, IK, and CALML5 were identified as significant prognostic markers for HCC. A prognostic model was developed that effectively stratified patients into risk groups, which correlated with survival. G6PD's role in immune modulation and its potential as a drug target were validated through biochemical assays and computational analyses. Functional assays in HepG2 cells confirmed that alterations in G6PD expression affect T cell activity, with knockdown enhancing IFN-γ production and overexpression inhibiting it, demonstrating G6PD's role in immune evasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study establishes lactate metabolism genes, particularly G6PD, as key prognostic markers in HCC. The validation of G6PD's immunomodulatory effects further supports its potential as a therapeutic target for strategies aimed at enhancing immune surveillance and treatment outcomes in HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of RIG-I is Critical for Responsiveness to IFN-α Plus Anti-PD-1 in Colorectal Cancer","authors":"Haihang Nie,&nbsp;Shilin Fang,&nbsp;Rui Zhou,&nbsp;Yifan Jia,&nbsp;Jingkai Zhou,&nbsp;Yumei Ning,&nbsp;Yali Yu,&nbsp;Yuntian Hong,&nbsp;Fei Xu,&nbsp;Qiu Zhao,&nbsp;Jiayan Nie,&nbsp;Fan Wang","doi":"10.1002/cam4.70802","DOIUrl":"10.1002/cam4.70802","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgrounds</h3>\u0000 \u0000 <p>Immunotherapy is a promising and effective approach that has achieved significant curative effects in colorectal cancer (CRC). Recently, retinoic acid-inducible gene I (RIG-I) has been shown to play a critical role in tumor immunity. However, the correlation between RIG-I and immunotherapy in CRC remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RIG-I expression was measured in CRC and normal samples based on analysis of the public databases, a tissue microarray, and CRC cell lines. The correlation between RIG-I and immune microenvironment was explored using well-established biological algorithms and in vitro and in vivo experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We discovered that RIG-I expression was downregulated in CRC compared with normal samples. The bioinformatic algorithms indicated that high RIG-I-expressing samples showed a positive correlation with IFN-α response and enrichment of antitumor immune cells, especially CD8+ T cells. Furthermore, knockdown of RIG-I expression efficiently reduced the cell death, STAT1 phosphorylation, and CXCL10/11 expression induced by IFN-α in CRC cells. Finally, an in vivo study showed that the infiltration of CD3+ CD8+ T cells was significantly decreased in the RIG-I knockout group. An animal model further confirmed that the inhibition of tumor growth induced by IFN-α plus anti-PD-1 therapy was dependent on RIG-I expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RIG-I is a promising biomarker for CRC immunotherapy, which provides a novel concept for combinatorial immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Performance Status, Inflammation, and Nutrition on the Impact of SGLT2 Inhibitors on Cancer Outcomes","authors":"Diego Rivas-Otero,&nbsp;Tomás González-Vidal,&nbsp;Pablo Agüeria-Cabal,&nbsp;Guillermo Ramos-Ruiz,&nbsp;Paula Jimenez-Fonseca,&nbsp;Carmen Lambert,&nbsp;Pedro Pujante Alarcón,&nbsp;Edelmiro Menéndez Torre,&nbsp;Miguel García-Villarino,&nbsp;Elías Delgado Álvarez","doi":"10.1002/cam4.70807","DOIUrl":"10.1002/cam4.70807","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sodium–glucose-linked transporter 2 inhibitors (SGLT2i) may have antitumor effects. Previous studies analyzing their role in mortality and progression did not account for potential confounders, including cancer treatment, performance status, inflammatory markers, and nutritional status. This study aims to evaluate the impact of SGLT2i treatment on mortality and progression while considering these potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cohort study was conducted. A total of 526 patients with cancer (302 women, mean age 64 years, range 40–79 years) were divided into two cohorts based on whether they were taking SGLT2i at the time of their cancer diagnosis and followed for 1 year or until death. All patients on SGLT2i were taking these drugs at standard clinical doses. Additional data collected included basic demographic variables, metabolic and lifestyle characteristics, cancer treatment received, performance status, inflammatory markers, and nutritional status. The primary endpoints were mortality and progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients taking SGLT2i at the time of cancer diagnosis (<i>n</i> = 41) were more likely to have type 2 diabetes, to be male, to be ever-smokers, and to be older than patients not taking SGLT2i. In univariate analyses, SGLT2i treatment at the time of cancer diagnosis was not associated with mortality or cancer progression. Instead, mortality and cancer progression were positively associated with a diagnosis of T2D, male sex, older age, heavy alcohol drinking, ever-smoker status, poor performance status, increased inflammation, malnutrition, tumor site, cancer stage, and lack of cancer treatment. After adjusting for these potential confounders, SGLT2i treatment was not significantly associated with mortality or cancer progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that the impact of SGLT2i treatment on cancer outcomes is limited under standard clinical dosing conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal Lipids in Cancer Progression and Metastasis","authors":"Dandugudumula Ramu,&nbsp;Eunjoo Kim","doi":"10.1002/cam4.70687","DOIUrl":"10.1002/cam4.70687","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metastasis is the primary cause of cancer mortality. It is responsible for 90% of all cancer-related deaths. Intercellular communication is a crucial feature underlying cancer metastasis and progression. Cancerous tumors secrete membrane-derived small extracellular vesicles (30–150 nm) into their extracellular milieu. These tiny organelles, known as exosomes, facilitate intercellular communication by transferring bioactive molecules. These exosomes harbor different cargos, such as proteins, nucleic acids, and lipids, that mediate multifaceted functions in various oncogenic processes. Of note, the amount of lipids in exosomes is multifold higher than that of other cargos. Most studies have investigated the role of exosomes' protein and nucleic acid content in various oncogenic processes, while the role of lipid cargo in cancer pathophysiology remains largely obscure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted an extensive literature review on the role of exosomes and lipids in cancer progression, specifically addressing the topic of exosomal lipids and their involvement in cancer metastasis and progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review aims to shed light on the lipid contents of exosomes in cancer metastasis. In this context, the role of exosomal lipids in signaling pathways, immunomodulation, and energy production for cancer cell survival provides insights into overcoming cancer progression and metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Perspectives on Impact of Weight and Weight Stigma on Breast and Cervical Cancer Treatment: A Qualitative Study","authors":"Jamie L. Sorensen,&nbsp;Michele M. West,&nbsp;Kathleen M. Robinson,&nbsp;Mary E. Charlton,&nbsp;Ingrid M. Lizarraga,&nbsp;Sarah H. Nash","doi":"10.1002/cam4.70823","DOIUrl":"10.1002/cam4.70823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Higher weight individuals report experiencing weight-based stigma in the healthcare setting; within the cancer continuum, the most robust evidence exists for cancer screening. More research is needed to understand whether and how higher weight patients experience weight stigma during cancer treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted semi-structured interviews with 15 breast and 15 cervical cancer survivors diagnosed 2017–2019 in Iowa who had a pre-diagnosis body mass index of 30+ kg/m² calculated from their driver's license height and weight. Interviews focused on whether individuals perceived being treated differently because of their weight in daily life, in healthcare, or during cancer treatment. Data were coded using a combination of inductive and deductive approaches, and analyzed using a multi-phase thematic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Almost all interviewees reported positive experiences during cancer treatment; several described their weight as never being an issue. Some identified weight stigma during cancer diagnosis or treatment that resulted in delayed diagnoses or changes in treatment. Many interviewees described situations where their weight was discussed negatively during cancer treatment, but most did not identify these as stigmatizing because their providers were only “concerned about [their] health.” Additional themes developed included experiencing environmental stigma, the discussion of cancer recurrence by providers only as it related to weight, and misconceptions of the causes and consequences of obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While several participants did not feel that their weight impacted cancer treatment, some reported experiences of weight stigma pre-diagnosis and during treatment. When individuals noted their weight was discussed during treatment, internalized bias may have impacted whether they considered these discussions stigmatizing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Pharmacokinetics, and Pharmacodynamics Evaluation of Ivonescimab, a Novel Bispecific Antibody Targeting PD-1 and VEGF, in Chinese Patients With Advanced Solid Tumors","authors":"Fenghua Wang,&nbsp;Xiaoli Wei,&nbsp;Yulong Zheng,&nbsp;Jing Wang,&nbsp;Jieer Ying,&nbsp;Xiaozhong Chen,&nbsp;Suxia Luo,&nbsp;Huiyan Luo,&nbsp;Xufang Yu,&nbsp;Benchao Chen,&nbsp;Lei Ma,&nbsp;Ruihua Xu","doi":"10.1002/cam4.70653","DOIUrl":"10.1002/cam4.70653","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ivonescimab (AK112) is a first-in-class bispecific antibody that simultaneously targets programmed death-1 (PD-1) and vascular endothelial growth factor (VEGF) with cooperative binding. We report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ivonescimab in patients suffered from advanced solid tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multicenter, open-label, dose-escalation, phase I study was conducted in five hospitals in China. Ivonescimab was used as a monotherapy. The dose of ivonescimab intravenously administered was 3, 5, 10, 20, and 30 mg/kg every 2 weeks (Q2W), and 10 and 20 mg/kg every 3 weeks (Q3W). Safety, PK, and PD of ivonescimab were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 59 patients treated in the study. Only one dose-limiting toxicity (DLT) occurred in 1 out of 9 patients in the 10 mg/kg Q2W cohort, indicating that no maximum tolerated dose was reached. Among the participants, 53 patients (89.8%) experienced treatment-related adverse events (TRAEs), with the most common being proteinuria (33.9%), aspartate aminotransferase elevation (27.1%), white blood cell count decrease (22.0%), alanine aminotransferase elevation (20.3%), and anemia (20.3%). Fourteen patients (23.7%) had ≥ Grade 3 TRAEs, and 7 patients (11.9%) experienced serious TRAEs. Notably, there were no reported deaths associated with the TRAEs, and no dose-dependent increase in adverse events was observed. The half-life of ivonescimab ranged from 5.0 to 7.3 days following single-dose administration across all dose levels. The serum concentrations of ivonescimab increased with escalating doses in an approximately dose-proportional manner. Following multiple doses, the accumulation ratio ranged from 1.1 to 1.7, suggesting mild accumulation of ivonescimab. The steady state was achieved after 5 doses. Ivonescimab occupancy on PD-1 sustained over 80% across the treatment period. Serum VEGF level was rapidly down-regulated after each administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with advanced solid tumors, ivonescimab monotherapy was well-tolerated and demonstrated a linear PK characteristics. PD profiles showed the promising potential of ivonescimab for the management of advanced solid tumors.</p>\u0000 \u0000 <p><b>Trial Registration:</b> ClinicalTrials.gov (NCT04597541)</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Mortality Rates Between Patients With Diffuse Large B Cell Lymphoma Surviving 5 Years After Initial Diagnosis and a Matched General Population Cohort","authors":"John Acquavella,&nbsp;Dóra Körmendiné Farkas,&nbsp;Henrik Toft Sørensen","doi":"10.1002/cam4.70800","DOIUrl":"10.1002/cam4.70800","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To determine whether mortality for patients with diffuse large B-cell lymphoma who survived 5 years (DLBCL5ys) returns thereafter to general population levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This population-based cohort study included Danish residents between January 1, 2000, and December 31, 2023. Information on diagnoses, comorbidities, and vital status came from Danish health and administrative registries. Analyses included 4164 DLBCL5yr patients—55% of incident patients—and 41,640 individuals from the general population matched 10:1 by exact birth year, sex, and the calendar year of achieving DLBCL5yr status. We used Cox proportional hazards models to compute matched mortality hazard ratios (HRs) and 95% confidence intervals (CIs) and controlled for comorbidities by adding Charlson comorbidity index scores to our models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mortality rates were elevated for DLBCL5yr patients soon after their 5-year survival date. The absolute difference in mortality was 20 deaths per 1000 person-years, and the HR adjusted for comorbidities was 1.5 (95% CI 1.4–1.6). Mortality was elevated similarly for men and women. The elevated mortality for DLBCL5yr patients varied in magnitude by age, calendar period, and comorbidity burden, and included excess mortality from DLBCL, cancers other than lymphoma, and respiratory diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found that mortality for DLBCL5yr patients did not return to general population levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}