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| Open AccessSingle cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer
Head and neck squamous cell carcinoma (HNSCC) is characterised with high heterogeneity and unfavourable prognosis. Here, the authors perform single cell transcriptomics to investigate the tumour microenvironment features of HNSCC initiation, progression, lymph node metastasis and recurrence.
- Z. L. Liu
- , X. Y. Meng
- & Y. He
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Article
| Open AccessSpatial relationships in the urothelial and head and neck tumor microenvironment predict response to combination immune checkpoint inhibitors
Spatial positioning of cells within the tumour microenvironment may have a function in the success of immune checkpoint immunotherapy (ICI). Here the authors analyse spatial relationships from immunohistochemistry samples prior to ICI therapy and show that CD8 T cell or macrophage proximity to cancer cells is associated with better responses.
- Alberto Gil-Jimenez
- , Nick van Dijk
- & Lodewyk F. A. Wessels
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Article
| Open AccessNeoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial
Neoadjuvant chemo-immunotherapy represents a therapeutic option for resectable head and neck squamous cell carcinoma (HNSCC). Here the authors report the results of a phase II trial of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced HNSCC.
- Di Wu
- , Yong Li
- & Xuekui Liu
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Article
| Open AccessPredictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab
Toripalimab with definitive chemoradiotherapy is a promising treatment strategy for esophageal squamous cell carcinoma. Here, the authors show that ctDNA positivity and bTMB are predictive of response in patients within the EC-CRT-001 phase II trial.
- Baoqing Chen
- , Shiliang Liu
- & Mian Xi
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Article
| Open AccessMicrobes translocation from oral cavity to nasopharyngeal carcinoma in patients
Oral microbes in non-oral locations are noted across various cancers. This study highlights the abnormal translocation of oral microbes to the nasopharynx, raising the risk of nasopharyngeal cancer by remodeling the tumor microenvironment and potentially influencing EBV infection.
- Ying Liao
- , Yan-Xia Wu
- & Wei-Hua Jia
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Article
| Open AccessTumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer
Tumor histocultures have been exploited as tools to predict response to cancer therapy. Here the authors report the development and testing of a tumor histoculture platform to study response to immune checkpoint inhibitors in head and neck squamous cell carcinoma.
- Nandini Pal Basak
- , Kowshik Jaganathan
- & Satish Sankaran
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Article
| Open AccessCamrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial
The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Here the authors report the results of a phase II clinical trial of camrelizumab (anti-PD1) and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma.
- Hu Liang
- , Yao-Fei Jiang
- & Yan-Qun Xiang
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Article
| Open AccessToripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial
Although most patients achieve complete response after standard-of-care treatment, residual disease in patients with nasopharyngeal carcinoma is associated with poor prognosis. Here the authors report the results of a phase 2 trial of toripalimab (anti-PD1) plus capecitabine for patients with residual nasopharyngeal carcinoma.
- Xun Cao
- , Hao-Yang Huang
- & Xing Lv
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Article
| Open AccessSpatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response
Oral squamous cell carcinoma is known to contain altered tumour cells within both the tumour core and leading edge. Here, the authors utilise spatial transcriptomics to characterise differences in gene expression and ligand-receptor architecture between areas of the tumour.
- Rohit Arora
- , Christian Cao
- & Pinaki Bose
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Article
| Open AccessEGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial
By using tumor-specific fluorescent tracers, fluorescence molecular imaging (FMI) can be used to visualize tumor tissues with high specificity. Here the authors report the results of a phase II trial to evaluate the diagnostic accuracy of an EGFR-targeted FMI for intraoperative margin assessment in patients with oral squamous cell carcinoma.
- Jaron G. de Wit
- , Jasper Vonk
- & Max J. H. Witjes
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Article
| Open AccessCamrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial
Combination of immune checkpoint inhibitors with anti-angiogenic targeted therapy has shown efficacy in some solid tumours. Here the authors report the results of a phase 2 trial of camrelizumab (anti-PD1) plus apatinib as a second-line or later-line treatment regimen in platinum-resistant (cohort 1) or PD-1 inhibitor-resistant (cohort 2) Recurrent/Metastatic Nasopharyngeal Carcinoma patients.
- Li Yuan
- , Guo-Dong Jia
- & Hai-Qiang Mai
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Article
| Open AccessClinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma
Dual PD-1 and CTLA-4 checkpoint blockade has proven effective in several cancer types. Here the authors report the results of a clinical trial of anti-PD1 (nivolumab) and anti-CTLA4 (ipilimumab) in patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma.
- Darren Wan-Teck Lim
- , Hsiang-Fong Kao
- & N. Gopalakrishna Iyer
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Article
| Open AccessSingle cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer
The role of keratinocyte subpopulations in the different phases of the viral cycle during HPV16 infection remains to be characterised. Here, single cell RNA sequencing of HPV16 infected and uninfected organoids identifies 12 distinct keratinocyte populations including an HPV-reprogrammed keratinocyte subpopulation that is linked to cancer.
- Mary C. Bedard
- , Tafadzwa Chihanga
- & Susanne I. Wells
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Article
| Open AccessNasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction
Response rates to immunotherapies in patients with nasopharyngeal carcinoma (NPC) are still limited. Here the authors show that tumor-restricted CD70 correlates with regulatory T cell abundance and suppressive activity in NPC and that CD70 blockade improves response to anti-PD1 in preclinical models.
- Lanqi Gong
- , Jie Luo
- & Xin-Yuan Guan
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Article
| Open AccessSingle cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis
The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis.
- Hong Sheng Quah
- , Elaine Yiqun Cao
- & N. Gopalakrishna Iyer
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Article
| Open AccessYBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
The understanding of molecular mechanisms in different subtypes of head and neck cancer (HNC) will define subtype-specific treatment options. Here the authors show that PI3K-phospho-YBX1 axis promotes tumour growth in basal subtype of HNC, while unphosphorylated YBX1 acts as a suppressor of metastasis in the mesenchymal subtype with inactive PI3K signalling.
- Yuchen Bai
- , Carolin Gotz
- & Charbel Darido
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Article
| Open AccessIntegrated transcriptome study of the tumor microenvironment for treatment response prediction in male predominant hypopharyngeal carcinoma
Many patients with hypopharyngeal carcinoma (HPC) do not respond to first-line combination therapy. Here, the authors analyse the tumour and the tumour microenvironment of HPC patients treated with combination therapy using single-cell RNA-seq, and train a classifier to distinguish responders based on cell type composition.
- Yang Zhang
- , Gan Liu
- & Zhigang Huang
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Article
| Open AccessThe TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma
TINCR encodes a p53-regulated ubiquitin-like microprotein expressed in stratified epithelia. Tincr loss promotes UVB-induced skin carcinogenesis in mice and deletions and mutations in human squamous cell carcinoma support a tumor suppressor role.
- Lucia Morgado-Palacin
- , Jessie A. Brown
- & Adolfo A. Ferrando
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Article
| Open AccessSingle-cell transcriptome profiling of the stepwise progression of head and neck cancer
Head and neck squamous cell carcinomas (HNSCCs) undergo a stepwise progression from normal tissues. In order to better understand the molecular mechanisms behind such progression, here the authors profile HNSCC tumors at different stages using single-cell RNA-seq, and observe the role of interactions with the tumor microenvironment.
- Ji-Hye Choi
- , Bok-Soon Lee
- & Chul-Ho Kim
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Article
| Open AccessTRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models
The molecular mechanisms determining the response to radiotherapy remain incompletely understood. Here, the authors demonstrate that the E3 ubiquitin ligase and intracellular Fc receptor, TRIM21, impairs CD8+ T cell responses in nasopharyngeal carcinoma tumour models following ionizing radiation.
- Jun-Yan Li
- , Yin Zhao
- & Na Liu
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Article
| Open AccessEvolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance
It is critical to understand the factors that are associated with nasopharyngeal carcinoma (NPC) progression, metastasis and response to therapy. Here, the authors analyse primary and metastatic NPC samples using bulk and single-cell sequencing, and find two distinct evolutionary routes that lead to metastasis.
- Mei Lin
- , Xiao-Long Zhang
- & Ming-Yuan Chen
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Article
| Open AccessDNA methylation-based classification of sinonasal tumors
Sinonasal tumour diagnosis can be complicated by the heterogeneity of disease and classification systems. Here, the authors use machine learning to classify sinonasal undifferentiated carcinomas into 4 molecular classe with differences in differentiation state and clinical outcome.
- Philipp Jurmeister
- , Stefanie Glöß
- & David Capper
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Article
| Open AccessConnecting multiple microenvironment proteomes uncovers the biology in head and neck cancer
The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures.
- Ariane F. Busso-Lopes
- , Leandro X. Neves
- & Adriana F. Paes Leme
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Article
| Open AccessComprehensive and clinically accurate head and neck cancer organs-at-risk delineation on a multi-institutional study
Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs.
- Xianghua Ye
- , Dazhou Guo
- & Tsung-Ying Ho
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Article
| Open AccessA nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer
Cisplatin is the most frequently used chemotherapeutic agent for the treatment of patients with oral cavity squamous cell carcinoma (OCSCC), however, systemic administration is often associated with dose limiting side effects. Here the authors design and test a nano-engineered patch system (PRV111) for the local delivery of cisplatin-loaded chitosan nanoparticles and report the results of a phase 1/2 clinical trial of PRV111 in patients with OCSCC.
- Manijeh Goldberg
- , Aaron Manzi
- & Evgeny Izumchenko
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Article
| Open AccessLymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC
Response rates to immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) remain low. Here the authors show that ablative treatment of tumor-draining regional lymphatics, a standard of care approach in patients, impairs the tumor response to ICI in preclinical HNSCC models.
- Robert Saddawi-Konefka
- , Aoife O’Farrell
- & J. Silvio Gutkind
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Article
| Open AccessEphB4 and ephrinB2 act in opposition in the head and neck tumor microenvironment
EphrinB2 and its receptor EphB4 are highly expressed in head and neck squamous cell carcinoma (HNSCC) and disrupting EphB4-ephrinB2 interaction generates sub-optimal outcomes. Here, compartmental targeting of EphB4 and ephrinB2 in HNSCC cancer cell and endothelial compartments suggests that ephrinB2 acts as a tumor promoter and EphB4 as a tumor suppressor.
- Shilpa Bhatia
- , Diemmy Nguyen
- & Sana D. Karam
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Article
| Open AccessA lncRNA signature associated with tumor immune heterogeneity predicts distant metastasis in locoregionally advanced nasopharyngeal carcinoma
Long noncoding RNAs (lncRNAs) can be used for the development of prognostic signatures to predict tumour metastasis. Here the authors identify an immune-associated nine-lncRNA signature for predicting metastasis in a multicentre cohort of locoregionally advanced nasopharyngeal cancer patients.
- Ye-Lin Liang
- , Yuan Zhang
- & Na Liu
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Article
| Open AccessCHMP2A regulates tumor sensitivity to natural killer cell-mediated cytotoxicity
Genetic alteration can render tumor cells resistant to immune cell-mediated killing. Here based on a genome-wide CRISPR screening, the authors show that expression of CHMP2A confers tumor cell resistance to NK cell-mediated cytotoxicity, mechanistically involving CHMP2A-dependent regulation of extracellular vesicle secretion.
- Davide Bernareggi
- , Qi Xie
- & Dan S. Kaufman
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Article
| Open AccessUSP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma
Radiotherapy is the mainstay treatment for nasopharyngeal carcinoma (NPC). Here the authors show that the deubiquitinase, USP44, increases radiosensitivity of NPC cells by promoting the degradation of Ku80, and thus enhancing the levels of DNA damage.
- Yang Chen
- , Yin Zhao
- & Na Liu
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Article
| Open AccessNeoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma
Immune checkpoint blockade has become standard care for patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC). Here the authors present the results of a non-randomized phase Ib/IIa trial, reporting safety and efficacy of neoadjuvant nivolumab monotherapy and nivolumab plus ipilimumab prior to standard-of-care surgery in patients with HNSCC. .
- Joris L. Vos
- , Joris B. W. Elbers
- & Charlotte L. Zuur
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Article
| Open AccessGermline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer
Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.
- Aida Ferreiro-Iglesias
- , James D. McKay
- & Paul Brennan
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Article
| Open AccessA comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma
Epstein-Barr virus (EBV) is associated with high risk for nasopharyngeal carcinoma (NPC). Here, the authors develop a comprehensive risk score that combines risk effects of EBV and human genetics for NPC risk stratification.
- Xiang Zhou
- , Su-Mei Cao
- & Miao Xu
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Article
| Open AccessCisplatin-mediated activation of glucocorticoid receptor induces platinum resistance via MAST1
Glucocorticoid receptor (GR) agonists - used in the treatment of solid malignant tumors to reduce inflammation - could potentially affect the anti-tumor activity of chemotherapy. Here, the authors identify a mechanism of cisplatin resistance observed with GR agonist treatment, and show the binding and activation of GR by cisplatin, which leads to MAST1 activation and subsequent MAPK re-activation.
- Chaoyun Pan
- , JiHoon Kang
- & Sumin Kang
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Article
| Open AccessWhole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape
The genomic characterisation of nasopharyngeal carcinoma (NPC) remains crucial. Here, the authors perform whole-genome sequencing for 70 NPCs with EBV gene expression, report the somatic alterations and EBV-mediated effects converging on NF-κB activation and immune escape and identify targetable homozygous MTAP deletions.
- Jeff P. Bruce
- , Ka-Fai To
- & Kwok-Wai Lo
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Article
| Open AccessTranscriptional super-enhancers control cancer stemness and metastasis genes in squamous cell carcinoma
Little is known on the transcriptional mechanisms that control cancer stem cell (CSC) self-renewal and stemness. Here the authors show superenhancers (SEs) play a role in the transcription of cancer stemness genes as well as prometastatic genes, thereby controlling their tumorigenic potential; disrupting SEs inhibited CSC self-renewal and eliminated CSCs.
- Jiaqiang Dong
- , Jiong Li
- & Cun-Yu Wang
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Article
| Open AccessB cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma
Recent studies have highlighted the importance of B cells and tertiary lymphoid structures (TLS) in the modulation of anti-tumor immune responses. Here, the authors characterize how HPV status influences the phenotype of tumor infiltrating B cells in patients with head and neck squamous cell carcinoma and demonstrate that TLS with germinal centres are associated with better survival.
- Ayana T. Ruffin
- , Anthony R. Cillo
- & Tullia C. Bruno
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Article
| Open AccessSTING enhances cell death through regulation of reactive oxygen species and DNA damage
The endoplasmic reticulum-localized adaptor STING regulates the innate immune response through its ability to sense DNA damage. Here the authors reveal that STING functions as a regulator of cellular ROS homeostasis and tumor cell susceptibility to reactive oxygen dependent, DNA damaging agents.
- Thomas J. Hayman
- , Marta Baro
- & Joseph N. Contessa
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Article
| Open AccessComprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma
The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.
- Lanqi Gong
- , Dora Lai-Wan Kwong
- & Xin-Yuan Guan
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Article
| Open AccessNeoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells
Different neoadjuvant therapies have been proposed to improve immunotherapy for cancer treatment. Here, the authors perform a phase Ib clinical trial where an agonist OX40 antibody provided prior to surgery is well tolerated and increases proliferation and activation of tumor antigen-specific T cells in head and neck cancer patients.
- Rebekka Duhen
- , Carmen Ballesteros-Merino
- & Andrew D. Weinberg
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Article
| Open AccessTumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution
Nasopharyngeal carcinoma is a diverse cancer characterised by a heterogeneous microenvironment. Here, the authors use single cell sequencing to analyse the tumour microenvironment in 10 nasopharyngeal carcinoma tumours and identify different cell types including immune-suppressive T regulatory, tolerogenic dendritic, and exhausted CD8 T cells.
- Yang Liu
- , Shuai He
- & Jin-Xin Bei
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Article
| Open AccessSomatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy
Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.
- Matt Lechner
- , Volker H. Schartinger
- & Valerie J. Lund
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Article
| Open AccessA multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
Alcohol and smoking are both associated with oral/oropharyngeal cancer risk, but independent effects are unclear given their relatedness. Here, the authors use multivariable Mendelian randomization to show that both alcohol and smoking are independently causal for oral/oropharyngeal cancer.
- Mark Gormley
- , Tom Dudding
- & Rebecca C. Richmond
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Article
| Open AccessCo-administered antibody improves penetration of antibody–dye conjugate into human cancers with implications for antibody–drug conjugates
Antibody-drug conjugates targeting high expression receptors can suffer from poor tumour penetration. Here, the authors use unconjugated antibody to improve the penetration of an antibody-dye conjugate in a clinical study, supporting further clinical investigation of the co-administration strategy.
- Guolan Lu
- , Naoki Nishio
- & Eben L. Rosenthal
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Article
| Open AccessLymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics
A non-destructive and efficient method for predicting the risk of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) patients is highly needed. Here, the authors develop a transfer learning radiomics model for preoperative prediction of LNM in patients with PTC in a multicenter scenario.
- Jinhua Yu
- , Yinhui Deng
- & Cai Chang
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Article
| Open AccessAn optimal posttreatment surveillance strategy for cancer survivors based on an individualized risk-based approach
Monitoring patients for the recurrence of cancer can be costly and it is important to devise the optimum strategy for a given cancer and population. Here, the authors use nasopharyngeal cancer as a model and show using patient data an optimal follow-up schedule to detect recurrence of the cancer.
- Guan-Qun Zhou
- , Chen-Fei Wu
- & Ying Sun
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Article
| Open AccessExploiting metabolic acidosis in solid cancers using a tumor-agnostic pH-activatable nanoprobe for fluorescence-guided surgery
It is well known that the pH of tumor tissue is lower than that of the corresponding normal adjacent tissue. Here, the authors report a clinical trial of a pH activatable nanoparticle for imaging tumours.
- F. J. Voskuil
- , P. J. Steinkamp
- & S. A. H. J. de Visscher
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Article
| Open AccessA common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma
The MET receptor is frequently activated in cancer. Here, the authors show that in head and neck and lung squamous carcinoma, a polymorphic MET variant enhances binding to HER2, resulting in activation of HER2 signalling and progression of the cancers.
- Li Ren Kong
- , Nur Afiqah Binte Mohamed Salleh
- & Boon Cher Goh
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Article
| Open AccessSyngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4
Tobacco use is one of the major risk factors for Head and neck squamous cell carcinoma (HNSCC). Here, the authors report an immune-competent syngeneic mouse model that mimics human tobacco-related HNSCC, and develops tumors in the tongue, and report a high response rate to anti-CTLA-4 therapy.
- Zhiyong Wang
- , Victoria H. Wu
- & J. Silvio Gutkind