British Journal of Cancer最新文献

{"title":"TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial","authors":"Patrick M. Boland, Sarbajit Mukherjee, Iman Imanirad, Namrata Vijayvergia, Seth D. Cohen, Medhavi Gupta, Renuka V. Iyer, Andrei Bakin, Jianxin Wang, Sarah Chatley, Beth Cahill, Deepak Vadehra, Kristopher Attwood, Howard S. Hochster, Christos Fountzilas","doi":"10.1038/s41416-024-02845-x","DOIUrl":"10.1038/s41416-024-02845-x","url":null,"abstract":"The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumour efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study. Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS). We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2–11.8) months (vs. 6 months in historical control, p = 0.018). The median overall survival was 16.5 (90% CI 9.8–17.5) months. Sixty-seven per cent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhoea, nausea, and vomiting). Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard-of-care therapy is warranted. ClinicalTrials.gov NCT04109924.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1290-1297"},"PeriodicalIF":6.4,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus molecular subtyping of metastatic colorectal cancer expands biomarker-directed therapeutic benefit for patients with CMS1 and CMS2 tumors","authors":"Saikat Chowdhury, Joanne Xiu, Jennifer R. Ribeiro, Theodore Nicolaides, Jian Zhang, W. Michael Korn, Kelsey A. Poorman, Heinz-Josef Lenz, John L. Marshall, Matthew J. Oberley, George W. Sledge Jr., David Spetzler, Scott Kopetz, John Paul Shen","doi":"10.1038/s41416-024-02826-0","DOIUrl":"10.1038/s41416-024-02826-0","url":null,"abstract":"We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939). The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan–Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant). CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors. A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1328-1339"},"PeriodicalIF":6.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidity in patients with cancer treated at The Christie","authors":"Azadeh Abravan, Corinne Faivre-Finn, Fabio Gomes, Marcel van Herk, Gareth Price","doi":"10.1038/s41416-024-02838-w","DOIUrl":"10.1038/s41416-024-02838-w","url":null,"abstract":"Comorbidities have been shown to impact the presentation and treatment of patients with cancers. This study investigates the prevalence and patterns of comorbidity in a pan-cancer cohort of patients treated at a large UK specialist cancer center over a 9-year period. A retrospective review of 77,149 patients from 01/01/2014 to 15/12/2022 was conducted using the Adult Comorbidity Evaluation 27 score (ACE-27) to assess the burden of comorbidities across 12 organ systems and an overall comorbidity burden. Binary and multinomial logistic regressions were utilized to evaluate the relationships between comorbidity incidence and demographic and socio-economic factors. At the time of diagnosis, 59.7% of patients had at least one comorbidity, with the highest prevalence in lung cancer and the lowest in brain/CNS and endocrine gland cancers. Cardiovascular comorbidities were the most frequent. Comorbidity severity was higher in patients from more deprived areas. Age and performance status were associated with a higher incidence of all comorbidities examined. Patients with advanced stage had a lower risk of having a severe comorbidity burden. Comorbidities are common across all cancers but are more prevalent in certain patient populations. Further research to understand the implications of comorbidities in cancer management is needed.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1279-1289"},"PeriodicalIF":6.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02838-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131892","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":"The scienthetic method: from Aristotle to AI and the future of medicine","authors":"Karim I. Budhwani","doi":"10.1038/s41416-024-02841-1","DOIUrl":"10.1038/s41416-024-02841-1","url":null,"abstract":"While AI holds immense potential for accelerating advances in oncology, we must be intentional in developing and applying these technologies responsibly, equitably, and ethically. One path forward is for cancer care providers and researchers to be among the architects of AI and its adoption in medicine. Given the limitations of traditional top-down, hypothesis-driven design in an exponentially expanding data universe, on one hand, and the danger of spiraling into artificial ignorance (ai) from rushing into a purely ‘synthetic’ method on the other, this article proposes a ‘scienthetic’ method that synergizes AI with human wisdom. Tracing philosophical underpinnings of the scientific method from Socrates, Plato, and Aristotle to the present, it examines the critical juncture at which AI stands to either augment or undermine new knowledge. The scienthetic method seeks to harness the power and capabilities of AI responsibly, equitably, and ethically to transcend the limitations of both the traditional scientific method and purely synthetic methods, by intentionally weaving machine intelligence together with human wisdom.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1247-1249"},"PeriodicalIF":6.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peritumoral tissue (PTT): increasing need for naming convention","authors":"Dzenis Koca, Behnoush Abedi-Ardekani, Joel LeMaoult, Laurent Guyon","doi":"10.1038/s41416-024-02828-y","DOIUrl":"10.1038/s41416-024-02828-y","url":null,"abstract":"Various terms are used to describe non-malignant tissue located in the proximity of a tumor, belonging to the organ from which the tumor originated. Traditionally, these tissues, sometimes called “normal adjacent tissue” have been used as controls in cancer studies, and were considered representative of morphologically healthy, non-cancerous tissue. However, with the advancement of OMIC technologies, such tissues are increasingly recognized to be distinct from both tumor and healthy tissues. Furthermore, properties, characteristics, and role of these tissues in cancer formation and progression is increasingly studied. In order to make future research in this area more harmonized and more accessible, as well as to counter the widespread perception of normalcy, we are advocating the need for standardized naming convention. For this purpose, we propose the use of neutral and comprehensive term “Peritumoral Tissue” along with the acronym “PTT”. While significant amount of data on these tissues are publicly available, reuse of such data remains limited due to a lack of information on sample collection procedures. In order to facilitate future reuse of the data, we suggest a list of features that should be documented during sample collection procedures. These recommendations can aid the definition of Standard Operating Procedures.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 7","pages":"1111-1115"},"PeriodicalIF":6.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02828-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119019","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":"Efficacy and safety evaluation of androgen deprivation therapy-based combinations for metastatic castration-sensitive prostate cancer: a systematic review and network meta-analysis","authors":"Tianqi Wang, Xiaoyu Wang, Guixin Ding, Hongquan Liu, Xiaohong Ma, Jian Ma, Yuanshan Cui, Jitao Wu","doi":"10.1038/s41416-024-02823-3","DOIUrl":"10.1038/s41416-024-02823-3","url":null,"abstract":"This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC). We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency. Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43–1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27–0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates. Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1363-1377"},"PeriodicalIF":6.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of clonal TP53 mutations with loss of heterozygosity on adjuvant chemotherapy and immunotherapy in gastric cancer","authors":"Yun Gu, Mengyao Sun, Hanji Fang, Fei Shao, Chao Lin, Hao Liu, He Li, Hongyong He, Ruochen Li, Jieti Wang, Heng Zhang, Jiejie Xu","doi":"10.1038/s41416-024-02825-1","DOIUrl":"10.1038/s41416-024-02825-1","url":null,"abstract":"This study aimed to reveal the effect of TP53 status on clinical outcomes and underlying mechanism in gastric cancer (GC) patients. TP53 status was divided into three groups according to genome sequencing, namely clonal mutations with LOH (C-LOH), clonal diploid or subclonal mutations (CD-SC), and wild type (WT). The p53 protein activity was divided into over-expression (OE), Null and WT according to immunohistochemical staining. Four cohorts, including the TCGA, SMC, ZSHS and FUSCC cohort, were analyzed for association between TP53 mutation status and clinical outcomes and the underlying mechanism. In TCGA cohort, TP53 CD-SC were associated with superior overall survival compared to TP53 C-LOH cases. GC patients could benefit from ACT only in TP53 CD-SC/ p53 OE and TP53/ p53 WT subgroups, and TP53 C-LOH subgroup demonstrated the worst response to pembrolizumab among three subgroups. Genomic and immunophenotypic deconvolution revealed that TP53 C-LOH, CD-SC and WT differed for genomic and immune-related features. TP53 C-LOH GCs with genomic instability and immune evasion phenotype have poor clinical outcomes in patients treated with ACT or immunotherapy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1320-1327"},"PeriodicalIF":6.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02825-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104503","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":"Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression","authors":"Bukuru D. Nturubika, Carlos M. Guardia, David C. Gershlick, Jessica M. Logan, Carmela Martini, Jessica K. Heatlie, Joanna Lazniewska, Courtney Moore, Giang T. Lam, Ka L. Li, Ben S-Y Ung, Robert D. Brooks, Shane M. Hickey, Andrew G. Bert, Philip A. Gregory, Lisa M. Butler, John J. O’Leary, Douglas A. Brooks, Ian R. D. Johnson","doi":"10.1038/s41416-024-02829-x","DOIUrl":"10.1038/s41416-024-02829-x","url":null,"abstract":"This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis. Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples. The roles of vesicular trafficking machinery were evaluated through over-expression and siRNA. The effects of R1881 treatment on lysosome vesicular trafficking was evaluated by RNA sequencing, protein quantification and fixed- and live-cell microscopy. Altered regulation of lysosomal trafficking genes/proteins was observed in prostate cancer tissue, with significant correlations for co-expression of vesicular trafficking machinery in Gleason patterns. The expression of trafficking machinery was associated with poorer patient outcomes. R1881 treatment induced changes in lysosomal distribution, number, and expression of lysosomal vesicular trafficking machinery in hormone-sensitive prostate cancer cells. Manipulation of genes involved in lysosomal trafficking events induced changes in lysosome positioning and cell phenotype, as well as differential effects on cell migration, in non-malignant and prostate cancer cells. These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1263-1278"},"PeriodicalIF":6.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02829-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104500","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":"Stimulation of cGAS-STING pathway as a challenge in the treatment of small cell lung cancer: a feasible strategy?","authors":"Giulia Miglietta, Marco Russo, Giovanni Capranico, Jessica Marinello","doi":"10.1038/s41416-024-02821-5","DOIUrl":"10.1038/s41416-024-02821-5","url":null,"abstract":"Lung cancer has a significant incidence among the population and, unfortunately, has an unfavourable prognosis in most cases. The World Health Organization (WHO) classifies lung tumours into two subtypes based on their phenotype: the Non-Small Cell Lung Cancer (NSCLC) and the Small Cell Lung Cancer (SCLC). SCLC treatment, despite advances in chemotherapy and radiotherapy, is often unsuccessful for cancer recurrence highlighting the need to develop novel therapeutic strategies. In this review, we describe the genetic landscape and tumour microenvironment that characterize the pathological processes of SCLC and how they are responsible for tumour immune evasion. The immunosuppressive mechanisms engaged in SCLC are critical factors to understand the failure of immunotherapy in SCLC and, conversely, suggest that new signalling pathways, such as cGAS/STING, should be investigated as possible targets to stimulate an innate immune response in this subtype of lung cancer. The full comprehension of the innate immunity of cancer cells is thus crucial to open new challenges for successful immunotherapy in treating SCLC and improving patient outcomes.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1567-1575"},"PeriodicalIF":6.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02821-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104505","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":"Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study","authors":"Shiro Takamatsu, R. Tyler Hillman, Kosuke Yoshihara, Tsukasa Baba, Muneaki Shimada, Hiroshi Yoshida, Hiroaki Kajiyama, Katsutoshi Oda, Masaki Mandai, Aikou Okamoto, Takayuki Enomoto, Noriomi Matsumura","doi":"10.1038/s41416-024-02837-x","DOIUrl":"10.1038/s41416-024-02837-x","url":null,"abstract":"Considerable interobserver variability exists in diagnosis of ovarian high-grade endometrioid carcinoma (HGEC) and high-grade serous carcinoma (HGSC) due to histopathological similarities. While homologous recombination deficiency (HRD) correlates with drug sensitivity in HGSC, the molecular features of HGEC are unclear. Fresh-frozen samples from 15 ovarian HGECs and 274 ovarian HGSCs in the JGOG-TR2 cohort were submitted to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array. We additionally analyzed 555 ovarian HGSCs from TCGA-OV and 287 endometrial high-grade carcinomas from TCGA-UCEC. Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4). C1 (n = 41) showed CCNE1 amplification and poor survival. C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively. C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression. Notably, C4 exhibited a normal endometrium-like DNA methylation profile, thus, defined as “HGEC-type” tumors, which were also identified in TCGA-OV and TCGA-UCEC. Ovarian “HGEC-type” tumors present a non-HRD status, favorable prognosis, and endometrial differentiation, possibly constituting a subset of clinically diagnosed HGSCs.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 8","pages":"1340-1349"},"PeriodicalIF":6.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}