Cancer Communications最新文献

{"title":"Rare germline ATM variants predispose to secondary cancer in chronic lymphocytic leukaemia patients","authors":"Anna Petrackova, Jirina Manakova, Romana Nesnadna, Zuzana Kubova, Tomas Papajik, Eva Kriegova","doi":"10.1002/cac2.70010","DOIUrl":"10.1002/cac2.70010","url":null,"abstract":"<p>Chronic lymphocytic leukaemia (CLL) has one of the strongest familial risks of all cancers, as evidenced by the eight-fold increased risk seen in relatives of CLL patients, yet much of the heritable risk remains unexplained [<span>1</span>]. Patients with CLL also have a high rate of secondary cancer, i.e., the development of second primary malignancy, compared to the general population, which may be explained by immune dysregulation due to CLL and/or its treatment, but also by environmental and genetic risk factors [<span>2</span>]. The development of second cancer in patients with CLL contributes to higher morbidity in these patients [<span>2</span>]. As the population of long-term CLL survivors expands due to novel agents used in therapy, the identification of patients with risk of developing the second cancer may help to improve longevity of CLL patients.</p><p>In this monocentric study, we aimed to assess whether patients with CLL carrying rare germline variants in <i>ATM</i> have a higher risk of familial CLL or a higher risk of cancer in first-degree relatives than patients without these variants. Next, we aimed to assess whether patients carrying rare <i>ATM</i> variants develop secondary cancer or develop CLL at an earlier age than patients without these variants, and whether these variants influence the time to first treatment (TTFT) and overall survival (OS) in patients with CLL. In this large cohort, we also sought to confirm our previous observation that rare variants in <i>ATM</i> are associated with the development of IGHV-unmutated CLL [<span>3</span>], which has a worse prognosis compared to IGHV-mutated disease.</p><p>A total of 629 patients with CLL were included in the study with a median follow-up of 6 years (range, 0.08-37.80; Supplementary Materials and Methods, Supplementary Table S1). Ten (1.6%) of these patients carried rare pathogenic (P) or likely pathogenic (LP) variants in <i>ATM</i> and 18 (2.9%) carried rare variant of uncertain significance (VUS) in <i>ATM</i>, all heterozygous (Supplementary Table S2, Figure 1). Patients harbouring P/LP <i>ATM</i> variants had a higher risk of secondary cancer (50.0% of patients; relative risk [RR], 2.88; 95% confidence interval [CI], 1.51-5.47; <i>P</i> = 0.001) than those without these variants (17.0%). Similarly, patients harbouring rare VUSes in <i>ATM</i> had a higher risk of secondary cancer (46.0% of patients; RR, 2.56; 95% CI, 1.48-4.41; <i>P</i> = 0.001) than those without these variants (17.0%). Half (7/14) of patients who carried these germline <i>ATM</i> variants and had secondary cancer were first diagnosed with CLL, while the other half (5/9) were first diagnosed with another malignancy. Secondary cancers were always of a different type, with the exception of prostate cancer, which occurred in 2 patients.</p><p>Regarding age at diagnosis of first malignancy in patients with secondary cancer, there was no significant difference between patients carrying rare P/LP ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"669-672"},"PeriodicalIF":20.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflections and insights into the evolution of restrictive eligibility criteria for cancer clinical trials in China and beyond","authors":"Huiyao Huang, Huilei Miao, Jinling Tang, Ning Li","doi":"10.1002/cac2.70007","DOIUrl":"10.1002/cac2.70007","url":null,"abstract":"<p>Trial eligibility criteria, which define an appropriate evaluable population through inclusion and exclusion criteria, are fundamental for reliable evidence and should be tailored to the question that the trial sets out to answer [<span>1</span>]. However, exclusion criteria for cancer trials have become increasingly restrictive over the years, with the median number increased from 21 in 1986 to 46 in 2016 [<span>2, 3</span>]. These restrictive exclusion criteria have created substantial barriers to patient access to novel therapies, hindered trial recruitment and limited the generalizability of trial results, presenting not only practical and scientific problem, but also raises important issues of equity that affect everyone [<span>4</span>].</p><p>While this longstanding issue has garnered widespread attention in the United States (US), research on the severity of restrictive criteria and efforts to modernize them in China remain scarce [<span>5</span>]. Our limited study revealed that the restriction rate for older patients aged over 75 years in cancer trials in China was 56.5%, which is more than 10 times higher than that of the US [<span>5</span>]. Meanwhile, significant shifts in patterns of exclusion criteria, such as brain metastases from conditionally excluded to not excluded, have been observed in the US since a joint recommendation on broadening cancer eligibility criteria was made in 2017 [<span>6</span>]. The above observations inspire us to understand the potential drivers behind the evolution of overly restrictive exclusion criteria, and provide insights into best practice towards modernizing eligibility criteria in China and beyond.</p><p>Regarding to the evolution of overly restrictive eligibility criteria, several fundamental factors should be emphasized. The fundamental consideration about who should be recruited is the future application of the results. Logically, those eligible for a trial should be those who are deemed beneficial from using the treatment in the future. However, when the approved indications are not impacted, sponsors and researchers tend to exclude weaker patients and recruit healthier ones due to excessive concerns about vulnerable populations and drug risk-benefit profiles. This tendency is evident in the fact that most cancer trials in the US enroll healthier patients, such as those with no brain metastases (77.4%), better performance status (PS) (65%) [<span>7</span>].</p><p>Exclusion criteria are often applied in series, meaning that participants meeting any one of the criteria are eliminated. However, many common criteria, when used alone may not represent manifestations of the underlying malignancy or the potential risk-benefit profiles. For instance, if a therapy does not undergo hepatic metabolism and is not expected to cause hepatic toxicity, strict hepatic function eligibility criteria may not be necessary, or there should be very broad entry criteria. Therefore, it is essential to consider the","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"673-676"},"PeriodicalIF":20.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma","authors":"Katia Mariniello, James F. H. Pittaway, Barbara Altieri, Kleiton Silva Borges, Irene Hadjidemetriou, Claudio Ribeiro, Gerard Ruiz-Babot, David S. Tourigny, Jiang A. Lim, Julie Foster, Julie Cleaver, Jane Sosabowski, Nafis Rahman, Milena Doroszko, Constanze Hantel, Sandra Sigala, Andrea Abate, Mariangela Tamburello, Katja Kiseljak-Vassiliades, Margaret Wierman, Charlotte Hall, Laila Parvanta, Tarek E. Abdel-Aziz, Teng-Teng Chung, Aimee Di Marco, Fausto Palazzo, Celso E. Gomez-Sanchez, David R. Taylor, Oliver Rayner, Cristina L. Ronchi, Carles Gaston-Massuet, Silviu Sbiera, William M. Drake, Emanuel Rognoni, Matthias Kroiss, David T. Breault, Martin Fassnacht, Leonardo Guasti","doi":"10.1002/cac2.70012","DOIUrl":"10.1002/cac2.70012","url":null,"abstract":"<p>Adrenocortical carcinoma (ACC) is a rare malignancy with no widely available biomarkers and commonly presents at later stages with a bleak prognosis [<span>1</span>]. Dysregulation of signaling pathways involved in the organogenesis and homeostasis of the adrenal cortex is implicated in its pathogenesis [<span>2</span>]. The paternally expressed, cleavable protein delta-like non-canonical Notch ligand 1 (DLK1) is expressed in rat adrenocortical progenitor cells [<span>3</span>] and in clusters of relatively undifferentiated cells in the human adrenal gland [<span>4</span>]. Its expression is rare in most adult human tissues but has been reported across various cancers, often associated with worse survival [<span>5</span>]. Here we define the role of DLK1 in adrenocortical development, self-renewal, and the development and progression of ACC.</p><p>Dlk1<sup>+</sup> cells were present in both the capsule and cortex during embryonic development but became restricted to the capsule postnatally in both male and female mice (Supplementary Figure S1), with minimal overlap in expression with Axin-2 (Wnt-active) cells, their early descendants, and platelet-derived growth factor receptor alpha (PDGFRα), a marker of mesenchymal stem/fibroblastic cells (Supplementary Figure S2). Dlk1 cells were rarely positive for Ki-67, whereas <i>Gli1</i> expression in the capsule, unlike Dlk1, remained high during development and throughout postnatal life (Supplementary Figure S3). Genetic lineage tracing using inducible <i>Dlk1<sup>CreERT2/+</sup></i>; <i>Rosa<sup>tdTomato/+</sup></i> mice showed that Dlk1<sup>+</sup> cells functioned as adrenocortical stem cells during development (Figure 1A-F), but were largely dormant postnatally and inactive during postnatal adrenocortical remodeling (Supplementary Figure S4).</p><p>Capsular-like cells are pathognomonic of subcapsular hyperplasia (SH), a histological hallmark in mouse adrenals that occurs spontaneously in aged females and in certain strains/transgenic models after gonadectomy (GDX) [<span>6</span>]. SH foci are thought to represent a morphological continuum progressing toward adrenocortical tumors. Dlk1 was not expressed in SH or in subsequent tumors in two GDX mouse models (Supplementary Figure S5). Moreover, spontaneous SH foci in aged mice were neither enriched in nor derived from Dlk1-expressing cells (Supplementary Figure S6), supporting the hypothesis that SH results from a de-differentiation event [<span>7</span>]. Interestingly, Dlk1 was re-expressed in an autochthonous mouse model of ACC, in which concomitant inactivation of <i>Trp53</i> and activation of <i>Ctnnb1</i>, driven by the aldosterone synthase promoter (<i>BPCre</i>) [<span>8</span>], leads to ACC formation with high penetrance. In 23 tumor samples from 17 mice (9 female), Dlk1 expression was low or absent in benign and pre-malignant tumors, moderate in localized ACC, and higher in metastatic disease, both in the primary tumors and in lung meta","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"663-668"},"PeriodicalIF":20.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low household income and income volatility increase risk of lung cancer: A nationwide retrospective cohort study","authors":"Chiwook Chung, Dong Wook Shin, Kyu Na Lee, Sei Won Lee, Kyungdo Han","doi":"10.1002/cac2.70011","DOIUrl":"10.1002/cac2.70011","url":null,"abstract":"<p>Low socioeconomic conditions, including low education, low income, manual or unskilled work, and unemployment, have been associated with increased lung cancer risks [<span>1, 2</span>]. Although some studies have identified low household status as a risk factor for lung cancer, they had some limitations in terms of their study design, including limited covariates in multivariate models, and cross-sectional assessment of income status, thereby failing to describe the association between income status change over time and lung cancer [<span>1, 2</span>]. Therefore, we investigated the association between longitudinal low household income status and lung cancer in the South Korean general population. We collected information on income status for 5 years to determine the change in household income status and income volatility. We also designed multivariate regression models with covariates including demographics, lifestyle behaviors, and comorbidities. Consequently, this study investigated the relationship between economic vulnerability, such as income volatility, and lung cancer risk.</p><p>We sampled 40% (4,910,068) of individuals who underwent a national health examination in 2012 (the index year). Among them, we included 3,816,680 individuals aged 30-65 years (economically active population). Thereafter, we excluded individuals with insufficient income information, identified with any cancer (any insurance claim with the International Classification of Diseases 10th Revision [ICD-10] codes for cancer [C00-97] and the critical illness registration code for cancer [V193]) before their health examination (all cancer wash-out), with insufficient medical records, and identified with any cancer within 1 year after the index date (1-year lag period, to exclude over-detection of cancer after the health examination). Finally, the remaining 3,361,091 eligible individuals started follow-up 1 year after the index date, until December 2022. The follow-up was terminated upon lung cancer development, death, or censor.</p><p>Lung cancer was identified using the ICD-10 code (C33 and C34) and matched with the critical illness registration program code (V193). The household income level was estimated based on subscribers’ monthly national health insurance premium, which is a proxy for household income. We categorized household income into quartiles (Q1 = lowest and Q4 = highest). Individuals receiving medical aid benefits (public assistance, the lowest 3% income) were assessed as a separate income category. To evaluate the temporal changes in household income status, we evaluated (1) cumulative number of years receiving medical aid (sustained low-income status) and (2) income volatility, defined as the intraindividual standard deviation (SD) of the percentage change in income (Q1 = the lowest and Q4 = the highest, Supplementary Figure S1), predicts income uncertainty and may limit health behaviors.</p><p>Covariates were collected from the health examination and ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"654-657"},"PeriodicalIF":20.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Older adults living with gastrointestinal cancers in 2021","authors":"Pojsakorn Danpanichkul, Yanfang Pang, Torlap Inkongngam, Kornnatthanai Namsathimaphorn, Krittameth Rakwong, Chuthathip Kaeosri, Benjamin Nah, Kwanjit Duangsonk, Nicole Shu Ying Tang, Neha Mittal, Donghee Kim, Mazen Noureddin, Michael B. Wallace, Amit G. Singal, Karn Wijarnpreecha, Ju Dong Yang","doi":"10.1002/cac2.70014","DOIUrl":"10.1002/cac2.70014","url":null,"abstract":"<p>The global average life expectancy is projected to rise to 80 years by 2040 [<span>1</span>]. Since cancer is closely linked to aging, its prevalence is expected to grow as the population ages. Advancements in cancer diagnosis and treatment have led to an increasing number of cancer survivors. In a 2021 consensus statement, the International Society for Geriatric Oncology updated its top priorities for improving care for older cancer patients [<span>2, 3</span>]. According to the Global Burden of Disease (GBD) study, there were over four million deaths from gastrointestinal (GI) cancer in 2021 [<span>4</span>].</p><p>The aging population, advancements in cancer management, and shifting risk factors are undoubtedly influencing the prevalence of GI cancers in older adults [<span>5</span>]. While aging has increasingly captured the attention of policymakers and stakeholders, epidemiological data on GI cancers in older adults remains limited. Older patients are also underrepresented in GI-specific clinical trials. This study aimed to estimate the global burden of GI cancers in older adults using the most recent GBD 2021 [<span>6</span>].</p><p>The general methods used for estimating disease burden in the GBD 2021 study, including GI cancer, have been detailed in previous publications [<span>4, 6</span>]. Briefly, data were sourced from population-based cancer registries, vital registration systems, and verbal autopsy studies (Supplementary Information S1). This GBD database defines older adults as individuals aged 70 and above. The GBD 2021 study utilized the International Classification of Disease-Tenth and Ninth Revision for GI cancers. We assessed the burden of various GI cancers in older adults, including colorectal, esophageal, liver, biliary tract, pancreatic, and gastric cancers. For liver cancer, we further analyzed the burden by five main etiologies: alcohol, chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, metabolic dysfunction-associated steatohepatitis (MASH), and other causes. Several statistical methods were applied to ensure data consistency, including misclassification correction, garbage code redistribution, and noise reduction algorithms. Mortality rates were evaluated using the Cause of Death Ensemble model (CODEm), which employed Bayesian geospatial regression to account for spatial relationships in the data. The detailed CODEm methodology is listed in Supplementary Information S1. Countries were classified based on their level of development using the sociodemographic index (SDI) (Supplementary Information S2).</p><p>The incidence, prevalence, and disability-adjusted life years (DALYs) (i.e., years of life lost plus years lost due to disability) estimates were reported with a 95% uncertainty interval (UI), calculated as the 2.5th and 97.5th percentiles from a posterior distribution of 1,000 draws. Broader UIs indicate higher uncertainty, typically resulting from limited or lower-quality dat","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"658-662"},"PeriodicalIF":20.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An open-label, single-arm, multicenter, phase II trial of bireociclib as monotherapy for heavily pretreated HR-positive, HER2-negative advanced breast cancer patients: BRIGHT-1 trial","authors":"Jiayu Wang,&nbsp;Qingyuan Zhang,&nbsp;Tao Sun,&nbsp;Huiping Li,&nbsp;Ying Cheng,&nbsp;Zhongsheng Tong,&nbsp;Huihui Li,&nbsp;Wei Li,&nbsp;Jingfen Wang,&nbsp;Yuee Teng,&nbsp;Xinhong Wu,&nbsp;Jing Cheng,&nbsp;Zhendong Chen,&nbsp;Zhengqiu Zhu,&nbsp;Li Wang,&nbsp;Mingming Liu,&nbsp;Xianghui Duan,&nbsp;Lingmei Xu,&nbsp;Binghe Xu","doi":"10.1002/cac2.70009","DOIUrl":"10.1002/cac2.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bireociclib (XZP-3287) is a novel selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, with a favorable safety profile demonstrated in preclinical and phase I studies. BRIGHT-1 aimed to further explore the efficacy and safety of bireociclib monotherapy in patients with locally advanced, recurrent or metastatic, hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR⁺/HER2⁻) breast cancer who had progressed on or after prior chemotherapy and endocrine therapy in advanced settings, without previous exposure to CDK4/6 inhibitors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this open-label phase II trial, eligible patients received bireociclib 480 mg twice daily (BID) until disease progression or intolerable toxicities. The primary endpoint was the confirmed objective response rate (ORR) assessed by an independent review committee (IRC). The secondary endpoints included progression-free survival (PFS), investigator-assessed ORR, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS), safety and the pharmacokinetic properties of bireociclib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 131 patients were enrolled. At data cutoff (July 31, 2023), the IRC-assessed ORR was 29.8% (95% confidence interval [CI], 22.1% to 38.4%), with a DCR of 73.3% (95% CI, 64.8% to 80.6%), CBR of 42.0% (95% CI, 33.4% to 50.9%) and a median DoR of 15.2 months (95% CI, 9.5 months to not reached). The median PFS was 11.0 months (95% CI, 7.3 months to 12.9 months) assessed by the IRC, and the median OS was 29.0 months (95% CI, 24.9 months to not reached). The most frequently reported treatment-emergent adverse events (TEAEs) of any grade were diarrhea (93.1%), neutrophil count decreased (87.0%), white blood cell decreased (86.3%), vomiting (78.6%), anemia (72.5%), and platelet count decreased (72.5%). The grade ≥3 TEAEs occurred in 109 (83.2%) patients. The most common grade ≥3 TEAEs were neutrophil count decreased (43.5%), white blood cell decreased (32.8%), hypokalemia (20.6%), and diarrhea (19.1%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Bireociclib monotherapy at 480 mg BID exhibited promising and sustained clinical activity, with no unexpected and acceptable toxicity in patients with recurrent or metastatic HR⁺/HER2⁻ breast cancer who had progressed on or after previous therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 6","pages":"640-653"},"PeriodicalIF":20.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant chemotherapy plus anlotinib in the treatment of resectable head and neck squamous cell carcinoma: A pilot phase II trial","authors":"Qianting He,&nbsp;Shuojin Huang,&nbsp;Dongxiao Tang,&nbsp;Congyuan Cao,&nbsp;Wanhang Zhou,&nbsp;Rongsong Ling,&nbsp;Jie Chen,&nbsp;Bokai Yun,&nbsp;Xin Zheng,&nbsp;Yanchen Li,&nbsp;Anxun Wang,&nbsp;Demeng Chen","doi":"10.1002/cac2.70006","DOIUrl":"10.1002/cac2.70006","url":null,"abstract":"<p>Head and neck squamous cell carcinoma (HNSCC) continues to be a major global health challenge, with limited survival improvements for patients with locally advanced (LA) or recurrent (R) disease [<span>1</span>]. Anlotinib, a novel orally administered small-molecule tyrosine kinase inhibitor (TKI) developed in China, targets a wide range of receptor tyrosine kinases (RTKs) [<span>2</span>]. Our previous studies have also manifested that anlotinib remarkably inhibited the proliferation of HNSCC cells both in vitro and in vivo, and presented promising clinical antitumor efficacy and tolerable safety profile in patients with oral squamous cell carcinoma (OSCC) [<span>3, 4</span>]. This prospective trial was designed to evaluate the clinical efficacy and safety of anlotinib combined with paclitaxel and cisplatin (TP) neoadjuvant therapy in patients with resectable HNSCC. Additionally, the mechanisms underlying the effects of anlotinib and neoadjuvant chemotherapy on HNSCC were investigated through spatial transcriptomics (STs) and multiplex immunohistochemistry (mIHC).</p><p>Between October 2022 and May 2023, 20 resectable HNSCC patients were enrolled (median age, 55; range, 27-73). Baseline demographics and disease characteristics are detailed in Supplementary Tables S1-S2. All patients received 3 cycles of neoadjuvant therapy, followed by surgery in 17 and maintenance therapy in 16. No patients were lost to follow-up (study flowchart in Figure 1A). After neoadjuvant therapy, 95.0% (19/20) achieved partial response (PR), and 5.0% (1/20) achieved complete response (CR), with an Objective response rate (ORR) of 100% (95% confidence interval [CI], 83.2-100). Figure 1B shows the waterfall plot of tumor size changes. Surgical resection was performed in 17 patients (LA, 12; R, 5) with a 100% R0 resection rate, one patient declined surgery due to financial constraints and the other two did not want to perform surgery as their tumors had almost regressed. Postoperative pathological efficacy (Supplementary Table S3) showed pathological complete response (pCR) and major pathological response (MPR) in 7 patients each (41.2%; 95% CI, 18.4-67.1). Among 11 with positive cervical lymph nodes, 6 achieved pCR (54.5%; 95% CI, 23.4-83.3). Imaging and pathological data of patient #14 with CR are shown in Figure 1C-D.</p><p>All patients were followed for at least one year. Treatment responses and durations are shown in Figure 1E. By May 15, 2024, 17 out of 20 patients were alive. Of the 3 deaths, 1 patient with LA declined further therapy for financial constraints after neoadjuvant treatment and died a year later, another patient with LA refused maintenance therapy after surgery and died within a year, while one patient with LA died in a traffic accident four months post-radiotherapy. Among the all 20 patients, 5 (4 with LA and 1 with R) experienced local recurrence within 1 year. Of the 17 patients with R0 resection, 4 (3 with LA and 1 with R) had a local recurrence","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 5","pages":"632-636"},"PeriodicalIF":20.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 45, Issue 2","authors":"","doi":"10.1002/cac2.12553","DOIUrl":"https://doi.org/10.1002/cac2.12553","url":null,"abstract":"<p>Cover Image © Rachaphak/Shutterstock</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 2","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter pylori CagA elevates FTO to induce gastric cancer progression via a “hit-and-run” paradigm","authors":"Bing He,&nbsp;Yiyang Hu,&nbsp;Yuyun Wu,&nbsp;Chao Wang,&nbsp;Limin Gao,&nbsp;Chunli Gong,&nbsp;Zhibin Li,&nbsp;Nannan Gao,&nbsp;Huan Yang,&nbsp;Yufeng Xiao,&nbsp;Shiming Yang","doi":"10.1002/cac2.70004","DOIUrl":"10.1002/cac2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection contributes significantly to gastric cancer (GC) progression. The intrinsic mechanisms of <i>H. pylori</i>-host interactions and their role in promoting GC progression need further investigation. In this study, we explored the potential role of fat mass and obesity-associated protein (FTO) in mediating Cytotoxin-associated gene A (CagA)-induced GC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effects of <i>H. pylori</i> infection on N⁶-methyladenosine (m⁶A) modification were evaluated in both human samples and GC cell lines. The function of FTO in the progression of GC was elucidated through in vitro and in vivo studies. A series of techniques, including methylated RNA immunoprecipitation sequencing, RNA sequencing, RNA binding protein immunoprecipitation, and chromatin immunoprecipitation assays, were utilized to investigate the mechanism by which FTO mediates the capacity of <i>cagA</i>-positive <i>H. pylori</i> to promote GC progression. Furthermore, the therapeutic potential of the FTO inhibitor meclofenamic acid (MA) in impeding GC progression was evaluated across GC cells, animal models, and human GC organoids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Infection with <i>cagA</i>-positive <i>H. pylori</i> upregulated the expression of <i>FTO</i>, which was essential for CagA-mediated GC metastasis and significantly associated with a poor prognosis in GC patients. Mechanistically, CagA delivered by <i>H. pylori</i> enhanced <i>FTO</i> transcription via Jun proto-oncogene. Elevated FTO induced demethylation of m⁶A and inhibited the degradation of heparin-binding EGF-like growth factor (HBEGF), thereby facilitating the epithelial-mesenchymal transition (EMT) process in GC cells. Interestingly, eradication of <i>H. pylori</i> did not fully reverse the increases in FTO and HBEGF levels induced by <i>cagA</i>-positive <i>H. pylori</i>. However, treatment with a combination of antibiotics and MA substantially inhibited <i>cagA</i>-positive <i>H. pylori</i>-induced EMT and prevented GC metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study revealed that FTO mediates the “hit-and-run” mechanism of CagA-induced GC progression, which suggests that the therapeutic targeting of FTO could offer a promising approach to the prevention of CagA-induced cancer progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 5","pages":"608-631"},"PeriodicalIF":20.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities","authors":"Dan Shan,&nbsp;Jinling Song,&nbsp;Yuqing Ren,&nbsp;Yuyuan Zhang,&nbsp;Yuhao Ba,&nbsp;Peng Luo,&nbsp;Quan Cheng,&nbsp;Hui Xu,&nbsp;Siyuan Weng,&nbsp;Anning Zuo,&nbsp;Shutong Liu,&nbsp;Xinwei Han,&nbsp;Jinhai Deng,&nbsp;Zaoqu Liu","doi":"10.1002/cac2.70005","DOIUrl":"10.1002/cac2.70005","url":null,"abstract":"<p>Copper, one of the essential nutrients for the human body, acts as an electron relay in multiple pathways due to its redox properties. Both deficiencies and excesses of copper lead to cellular fragility. Therefore, it can manifest pro- and anti-cancer properties in tumors. Therefore, it is crucial to clarify the copper activity within the cell. We have thoughtfully summarized the metabolic activities of copper from a macro and micro perspective. Cuproptosis, as well as other forms of cell death, is directly or indirectly interfered with by Cu²⁺, causing cancer cell death. Meanwhile, we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes. In addition, copper has been found to be involved in multiple pathways within the metastasis of cancer cells. Given the complexity of copper's role, we are compelled to ask: is copper a friend or a foe? Up to now, copper has been used in various clinical applications, including protocols for measurement of copper concentration and bioimaging of radioactive ⁶⁴Cu. But therapeutically it is still a continuation of the old medicine, and new possibilities need to be explored, such as the use of nanomaterials. Some studies have also shown that copper has considerable interventional power in metabolic cancers, which provides the great applications potential of copper therapy in specific cancer types. This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress, cell death, and tumor metastasis, and points out the value of its application in specific cancer types, summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs, and emphasizes the prospects for the application of nano-copper.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"45 5","pages":"577-607"},"PeriodicalIF":20.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}