Koen Zwart, Sietske C M W van Nassau, Frederieke H van der Baan, Miriam Koopman, Petur Snaebjornsson, Anna J van Gestel, Geraldine R Vink, Jeanine M L Roodhart
BACKGROUND: Encorafenib-cetuximab has been approved for pretreated BRAFV600E -mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results. METHODS: This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected...
May 20, 2024: British Journal of Cancer
Dandan Zhang, Dongxian Jiang, Liping Jiang, Jiakang Ma, Xiaobing Wang, Xingyu Xu, Ziqiang Chen, Mengping Jiang, Wenjing Ye, Jie Wang, Weida Meng, Wenqing Qiu, Yingyong Hou, Jing Huang, Yuchen Jiao, Yun Liu, Zhihua Liu
BACKGROUND: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance. METHODS: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses...
May 18, 2024: British Journal of Cancer
Kaina Chen, Timothy W H Shuen, Pierce K H Chow
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. The emergence of combination therapy, atezolizumab (anti-PDL1, immune checkpoint inhibitor) and bevacizumab (anti-VEGF) has revolutionised the management of HCC. Despite this breakthrough, the best overall response rate with first-line systemic therapy is only about 30%, owing to intra-tumoural heterogeneity, complex tumour microenvironment and the lack of predictive biomarkers. Many groups have attempted to classify HCC based on the immune microenvironment and have consistently observed better outcomes in immunologically "hot" HCC...
May 17, 2024: British Journal of Cancer
Warapen Treekitkarnmongkol, Vandna Shah, Kazuharu Kai, Hiroshi Katayama, Justin Wong, Farah A Ladha, Tristian Nguyen, Brian Menegaz, Wei Lu, Fei Yang, Barbara Mino, Ximing Tang, Mihai Gagea, Harsh Batra, Maria Gabriela Raso, Ignacio I Wistuba, Savitri Krishnamurthy, Sarah E Pinder, Elinor J Sawyer, Alastair M Thompson, Subrata Sen
BACKGROUND: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS. METHODS: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts. RESULTS: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score...
May 17, 2024: British Journal of Cancer
Hiroko Minatogawa, Naoki Izawa, Takako Eguchi Nakajima
No abstract text is available yet for this article.
May 15, 2024: British Journal of Cancer
Umberto Malapelle, Natasha Leighl, Alfredo Addeo, Dov Hershkovitz, Maximilian J Hochmair, Ola Khorshid, Florian Länger, Filippo de Marinis, Nir Peled, Brandon S Sheffield, Egbert F Smit, Santiago Viteri, Jürgen Wolf, Filippo Venturini, Richard M O'Hara, Christian Rolfo
Non-small cell lung cancer is a heterogeneous disease and molecular characterisation plays an important role in its clinical management. Next-generation sequencing-based panel testing enables many molecular alterations to be interrogated simultaneously, allowing for comprehensive identification of actionable oncogenic drivers (and co-mutations) and appropriate matching of patients with targeted therapies. Despite consensus in international guidelines on the importance of broad molecular profiling, adoption of next-generation sequencing varies globally...
May 15, 2024: British Journal of Cancer
Hideyuki Masui, Kenji Kawada, Yoshiro Itatani, Hideyo Hirai, Yuki Nakanishi, Yoshiyuki Kiyasu, Keita Hanada, Michio Okamoto, Wataru Hirata, Yasuyo Nishikawa, Naoko Sugimoto, Takuya Tamura, Yoshiharu Sakai, Kazutaka Obama
BACKGROUND: Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked. METHODS: We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1-/- , Cxcr2-/- or Ccr1-/- Cxcr2-/- mice...
May 15, 2024: British Journal of Cancer
Baknoon Ham, Su Yeon Kim, Young-Ae Kim, DoYeon Han, Taehyun Park, Sumin Cha, SungWook Jung, Jong Hyeok Kim, Gisung Park, Gyungyub Gong, Hee Jin Lee, Junyoung Shin
BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood...
May 15, 2024: British Journal of Cancer
Thomas Aparicio, Julie Henriques, Magali Svrcek, Aziz Zaanan, Sylvain Manfredi, Andrea Casadei-Gardini, David Tougeron, Jean-Marc Gornet, Marine Jary, Eric Terrebonne, Guillaume Piessen, Pauline Afchain, Cédric Lecaille, Marc Pocard, Thierry Lecomte, Margherita Rimini, Frédéric Di Fiore, Valérie Le Brun Ly, Stefano Cascinu, Dewi Vernerey, Pierre Laurent Puig
BACKGROUND: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS: A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease...
May 14, 2024: British Journal of Cancer
Peter W T Lee, Tatsuya Suwa, Minoru Kobayashi, Hui Yang, Lina R Koseki, Satoshi Takeuchi, Christalle C T Chow, Takaaki Yasuhara, Hiroshi Harada
BACKGROUND: Cancer cells in severely hypoxic regions have been reported to invade towards tumour blood vessels after surviving radiotherapy in a postirradiation reoxygenation- and hypoxia-inducible factor (HIF)-dependent manner and cause recurrence. However, how HIF induces invasiveness of irradiated and reoxygenated cancer cells remains unclear. METHODS: Here, we identified human minor histocompatibility antigen 1 (HMHA1), which has been suggested to function in cytoskeleton dynamics and cellular motility, as a responsible factor and elucidated its mechanism of action using molecular and cellular biology techniques...
May 13, 2024: British Journal of Cancer
Nathalie C Støer, Siri Vangen, Deependra Singh, Renée T Fortner, Solveig Hofvind, Giske Ursin, Edoardo Botteri
BACKGROUND: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. METHODS: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. RESULTS: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12...
May 13, 2024: British Journal of Cancer
Andrew J Hayes, Ioanna F Nixon, Dirk C Strauss, Beatrice M Seddon, Anant Desai, Charlotte Benson, Ian R Judson, Adam Dangoor
Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues and can occur almost anywhere in the body. Their rarity, and the heterogeneity of subtype and location, means that developing evidence-based guidelines is complicated by the limitations of the data available. This makes it more important that STS are managed by expert multidisciplinary teams, to ensure consistent and optimal treatment, recruitment to clinical trials, and the ongoing accumulation of further data and knowledge. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field...
May 11, 2024: British Journal of Cancer
Hyein Jeong, Jaemoon Koh, Sehui Kim, Seung Geun Song, Soo Hyun Lee, Youngjoo Jeon, Chul-Hwan Lee, Bhumsuk Keam, Se-Hoon Lee, Doo Hyun Chung, Yoon Kyung Jeon
BACKGROUND: We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy. METHODS: PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed...
May 10, 2024: British Journal of Cancer
Nektarios A Valous, Ferdinand Popp, Inka Zörnig, Dirk Jäger, Pornpimol Charoentong
Multi-omics experiments at bulk or single-cell resolution facilitate the discovery of hypothesis-generating biomarkers for predicting response to therapy, as well as aid in uncovering mechanistic insights into cellular and microenvironmental processes. Many methods for data integration have been developed for the identification of key elements that explain or predict disease risk or other biological outcomes. The heterogeneous graph representation of multi-omics data provides an advantage for discerning patterns suitable for predictive/exploratory analysis, thus permitting the modeling of complex relationships...
May 10, 2024: British Journal of Cancer
Valentina Angerilli, Giovanna Sabella, Michele Simbolo, Vincenzo Lagano, Giovanni Centonze, Marco Gentili, Alessandro Mangogna, Jorgelina Coppa, Giada Munari, Gianluca Businello, Chiara Borga, Francesca Schiavi, Sara Pusceddu, Rita Leporati, Simone Oldani, Matteo Fassan, Massimo Milione
BACKGROUND: High-grade gastro-entero-pancreatic neoplasms (HG GEP-NENs) can be stratified according to their morphology and Ki-67 values into three prognostic classes: neuroendocrine tumors grade 3 (NETs G3), neuroendocrine carcinomas with Ki-67 < 55% (NECs <55) and NECs with Ki-67 ≥ 55% (NECs ≥55). METHODS: We analyzed a cohort of 49 HG GEP-NENs by targeted Next-Generation Sequencing (TrueSight Oncology 500), RNA-seq, and immunohistochemistry for p53, Rb1, SSTR-2A, and PD-L1...
May 10, 2024: British Journal of Cancer
Marlou-Floor Kenkhuis, Stephanie Stelten, Yvonne Aw Hartman, Calvin G Brouwer, Marieke R Ten Tusscher, Luc Rcw van Lonkhuijzen, Gemma G Kenter, Willemien J van Driel, Renate M Winkels, Ruud Lm Bekkers, Nelleke Pb Ottevanger, Meeke Hoedjes, Laurien M Buffart
BACKGROUND: Guidelines recommend to include exercise and dietary advice in standard care for patients with cancer, based on evidence primarily derived from patients with breast cancer. Its applicability to patients with ovarian cancer is uncertain due to differences in patient characteristics and treatments. The PADOVA trial examined the effectiveness of a combined exercise and dietary intervention on fat-free mass (FFM), physical functioning, and fatigue. METHODS: In total, 81 patients with ovarian cancer were randomised to the exercise and dietary intervention (n = 40) or control (n = 41) group...
May 8, 2024: British Journal of Cancer
Marc Oliva, Alya Heirali, Geoffrey Watson, Ashley M Rooney, Kyla Cochrane, Sarah Jennings, Rachel Taylor, Minge Xu, Ali Hosni, Andrew Hope, Scott V Bratman, Douglas Chepeha, Ilan Weinreb, Bayardo Perez-Ordonez, Ricard Mesia Nin, John Waldron, Wei Xu, Aaron R Hansen, Lillian L Siu, Bryan Coburn, Anna Spreafico
BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation. METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing...
May 7, 2024: British Journal of Cancer
Itamar Averbuch, Assaf Moore, Ethan B Ludmir, Gal Markel, Tomer Meirson
BACKGROUND: Metastasis-directed therapy (MDT) with stereotactic body radiotherapy (SBRT) is emerging as an effective therapeutic option for oligometastatic disease (OMD). However, a lack of phase III data, consensus guidelines, and toxicity concerns limit its widespread use. Randomized controlled trials (RCTs) routinely report hazard ratios (HRs) and medians that lack clear clinical and robust interpretation. Restricted-mean survival time (RMST) is the duration of time a patient is expected to survive over the follow-up period, providing a robust and interpretable alternative...
May 6, 2024: British Journal of Cancer
Sara Santagata, Giuseppina Rea, Anna Maria Bello, Anna Capiluongo, Maria Napolitano, Sonia Desicato, Alessandra Fragale, Crescenzo D'Alterio, Anna Maria Trotta, Caterina Ieranò, Luigi Portella, Francesco Persico, Marilena Di Napoli, Salvatore Di Maro, Florinda Feroce, Rosa Azzaro, Lucia Gabriele, Nicola Longo, Sandro Pignata, Sisto Perdonà, Stefania Scala
BACKGROUND: Tregs trafficking is controlled by CXCR4. In Renal Cell Carcinoma (RCC), the effect of the new CXCR4 antagonist, R54, was explored in peripheral blood (PB)-Tregs isolated from primary RCC patients. METHODS: PB-Tregs were isolated from 77 RCC patients and 38 healthy donors (HDs). CFSE-T effector-Tregs suppression assay, IL-35, IFN-γ, IL-10, TGF-β1 secretion, and Nrp-1+ Tregs frequency were evaluated. Tregs were characterised for CTLA-4, PD-1, CD40L, PTEN, CD25, TGF-β1, FOXP3, DNMT1 transcriptional profile...
May 4, 2024: British Journal of Cancer
Lynne Lohfeld, Meenakshi Sharma, Damien Bennett, Anna Gavin, Sinéad T Hawkins, Gareth Irwin, Helen Mitchell, Siobhan O'Neill, Charlene M McShane
The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment...
May 4, 2024: British Journal of Cancer
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