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| 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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| 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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| 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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| Open AccessA pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma
In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.
- Wu-tong Ju
- , Rong-hui Xia
- & Lai-ping Zhong
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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 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 AccessDisruption of the HER3-PI3K-mTOR oncogenic signaling axis and PD-1 blockade as a multimodal precision immunotherapy in head and neck cancer
There is an unmet need to improve the response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma (HNSCC). Here the authors show that aberrant HER3 activation sustains the proliferation of PIK3CA wild type HNSCC cells and that HER3 inhibition increases response to PD-1 blockade in HNSCC preclinical models.
- Zhiyong Wang
- , Yusuke Goto
- & J. Silvio Gutkind
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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 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 AccessGenomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology
Modelling oral squamous cell carcinoma (OSCC) is a complex endeavour. Here, the authors provide a comprehensive analysis of an OSCC mouse model and show its mutational signatures mirror human OSCC, providing insights into OSCC clonal dynamics, the microenvironment and evolution.
- Inês Sequeira
- , Mamunur Rashid
- & Fiona M. Watt
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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 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
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Article
| Open AccessCombining discovery and targeted proteomics reveals a prognostic signature in oral cancer
Oral cancer has region-specific histopathological and molecular characteristics, complicating its classification by the standard tumor-node-metastasis system. Here, the authors combine discovery and targeted proteomics with IHC to identify region-specific and saliva biomarkers for oral cancer prognosis.
- Carolina Moretto Carnielli
- , Carolina Carneiro Soares Macedo
- & Adriana Franco Paes Leme
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Article
| Open AccessImmunomodulatory role of Keratin 76 in oral and gastric cancer
Keratin 76 (Krt76) is an epithelial differentiation marker that is downregulated in oral squamous cell carcinomas, correlating with poor prognosis. Here the authors show that genetic ablation of Krt76 in a mouse model results in increased susceptibility to carcinogenesis via enhanced accumulation of Tregs.
- Inês Sequeira
- , Joana F. Neves
- & Fiona M. Watt
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Article
| Open AccessFbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma
Fbxo4 tumour suppressor is part of a SCF E3 ligase which has two known substrates. Here, the authors identify Fxr1 as a substrate of SCFFbxo4 and identify an inherent regulatory feedback loop in head and neck squamous cell carcinoma that results in the bypass of senescence and neoplastic progression.
- Shuo Qie
- , Mrinmoyee Majumder
- & J. Alan Diehl
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Article
| Open AccessAPOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism
Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.
- Ting-Wen Chen
- , Chi-Ching Lee
- & Yu-Sun Chang
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Article
| Open AccessLong noncoding RNA LncHIFCAR/MIR31HG is a HIF-1α co-activator driving oral cancer progression
Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNAMIR31HGas a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.
- Jing-Wen Shih
- , Wei-Fan Chiang
- & Hsing-Jien Kung
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Article |
Somatic mutations in arachidonic acid metabolism pathway genes enhance oral cancer post-treatment disease-free survival
Chemical inhibitors of the tumour-progression promoting arachidonic acid metabolism pathway prolong post-treatment survival of cancer patients. Here the authors analyse sequence variation in oral cancer patients and show that loss-of-function mutations in this pathway prolong survival.
- Nidhan K. Biswas
- , Subrata Das
- & Partha P. Majumder
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Article
| Open AccessMutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups
Gingivo-buccal oral squamous cell carcinoma (OSCC-GB) is the leading cancer among males in India. Here, the authors carry out exome sequencing and recurrence testing in patients with OSCC-GB and highlight genes and biological pathways associated with the disease.
- Arindam Maitra
- , Nidhan K. Biswas
- & D. Sutradhar