TNO155 is a selective SHP2 inhibitor to target -dependent oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is known to be driven by multiple intricated receptor tyrosine kinases (RTKs) including EGFR, PI3K/AKT and MAPK signaling pathways. However, whilst targeting EGFR with cetuximab has been approved for the treatment of OSCC, other single-agent inhibitors of the RTKs have shown modest effects in improving survival. From the genome-wide CRISPR/Cas9 screen on 21 OSCC cell lines, we have identified among the top essential genes in OSCC.

High TNF and NF-κB Pathway Dependency Are Associated with AZD5582 Sensitivity in OSCC via CASP8-Dependent Apoptosis.

Mechanistically guided drug repurposing has been made possible by systematically integrating pharmacologic and CRISPR-Cas9 screen data. Our study discovers the biomarker and cell death mechanisms underpinning sensitivity toward AZD5582, an antagonist of the inhibitor of apoptosis family protein. Our findings have important implications for improving future trial design for patients with OSCC using this emerging drug class.

Establishment and Characterization of an Epstein-Barr Virus-positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma.

Unlabelled: Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue.

Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer.

Unlabelled: The survival rate for patients with head and neck cancer (HNC) diagnosed with cervical lymph node (cLN) or distant metastasis is low. Genomic alterations in the HRAS oncogene are associated with advanced tumor stage and metastasis in HNC. Elucidation of the molecular mechanisms by which mutated HRAS (HRASmut) facilitates HNC metastasis could lead to improved treatment options for patients.

Time-to-Treatment of Oral Cancer and Potentially Malignant Oral Disorders: Findings in Malaysian Public Healthcare.

This study aims to evaluate the time-to-treatment of oral cancer and potentially malignant oral disorders (PMOD) in a Malaysian public healthcare setting while exploring its contributing factors. It consists of (1) a cross-sectional patient survey to quantify time to seek care and barriers faced, and (2) a retrospective medical record abstraction to determine treatment and management intervals. Time intervals were aggregated and analyzed by their primary contributor—patient, professional, or healthcare system.

Transcriptional analysis highlights three distinct immune profiles of high-risk oral epithelial dysplasia.

Oral potentially malignant disorders (OPMD) are precursors of oral squamous cell carcinoma (OSCC), and the presence of oral epithelial dysplasia (OED) in OPMD confers an increased risk of malignant transformation. Emerging evidence has indicated a role for the immune system in OPMD disease progression; however, the underlying immune mechanisms remain elusive. In this study, we used immune signatures established from cancer to delineate the immune profiles of moderate and severe OED, which are considered high-risk OPMD.

Household Catastrophic Health Expenditure from Oral Potentially Malignant Disorders and Oral Cancer in Public Healthcare of Malaysia.

Objective: Oral cancer causes a significant disease burden and financial distress, especially among disadvantaged groups. While Malaysia has achieved universal health coverage via its highly subsidized public healthcare, patient and family expenditure for treatment of oral potentially malignant disorders (OPMD) and oral cancer remains a concern in the equitability of care. This study thus aims to estimate household out-of-pocket (OOP) expenditures and the extent of catastrophic healthcare expenditure (CHE) while identifying its predictors.

Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g.

Image collection and annotation platforms to establish a multi-source database of oral lesions.

Objective: To describe the development of a platform for image collection and annotation that resulted in a multi-sourced international image dataset of oral lesions to facilitate the development of automated lesion classification algorithms.

Materials And Methods: We developed a web-interface, hosted on a web server to collect oral lesions images from international partners. Further, we developed a customised annotation tool, also a web-interface for systematic annotation of images to build a rich clinically labelled dataset.

Rational Combinations of Targeted Therapy and Immune Checkpoint Inhibitors in Head and Neck Cancers.

Immunotherapy, especially the immune checkpoint inhibitors (ICIs) such as the pembrolizumab and nivolumab have contributed to significant improvements in treatment outcomes and survival of head and neck cancer (HNC) patients. Still, only a subset of patients benefits from ICIs and hence the race is on to identify combination therapies that could improve response rates. Increasingly, genetic alterations that occur within cancer cells have been shown to modulate the tumor microenvironment resulting in immune evasion, and these have led to the emergence of trials that rationalize a combination of targeted therapy with immunotherapy.

Barriers to early detection and management of oral cancer in the Asia Pacific region.

Objective: Oral cancer is amenable to early detection but remains a prominent cause of mortality in the Asia Pacific region. This study aimed to identify barriers to early detection and management of oral cancer in the Asia Pacific region.

Methods: A mixed-methods approach was employed triangulating findings from a survey and focus groups.

Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis.

Effective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC.

DNA Vaccines Targeting Novel Cancer-Associated Antigens Frequently Expressed in Head and Neck Cancer Enhance the Efficacy of Checkpoint Inhibitor.

HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs).

Provider cost of treating oral potentially malignant disorders and oral cancer in Malaysian public hospitals.

Oral cancer has been recognized as a significant challenge to healthcare. In Malaysia, numerous patients frequently present with later stages of cancers to the highly subsidized public healthcare facilities. Such a trend contributes to a substantial social and economic burden.

High referral accuracy for oral cancers and oral potentially malignant disorders using telemedicine.

Objective: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral.

Subjects And Methods: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included.

An Overview on Betel Quid and Areca Nut Practice and Control in Selected Asian and South East Asian Countries.

Areca nut (AN) and betel quid (BQ) chewing are ancient practices followed by an extensive proportion of the world's population. These practices are endemic in larger parts of South and Southeast Asia and selected Western Pacific countries. The prevalence of these habits varies across regions, age, gender, cultural practice, and socioeconomic status groups.

Label-Free, High-Throughput Assay of Human Dendritic Cells from Whole-Blood Samples with Microfluidic Inertial Separation Suitable for Resource-Limited Manufacturing.

Microfluidics technology has not impacted the delivery and accessibility of point-of-care health services, like diagnosing infectious disease, monitoring health or delivering interventions. Most microfluidics prototypes in academic research are not easy to scale-up with industrial-scale fabrication techniques and cannot be operated without complex manipulations of supporting equipment and additives, such as labels or reagents. We propose a label- and reagent-free inertial spiral microfluidic device to separate red blood, white blood and dendritic cells from blood fluid, for applications in health monitoring and immunotherapy.

The establishment of the Asia-Pacific Oral Cancer Network-Inaugural stakeholders' Meeting.

The majority of oral cancer cases occur in Asia and the incidence is expected to continue to rise. Oral cancer is amenable to early detection through visual oral examination yet in many Asian countries, the disease presents at a late stage. The barriers to early detection are similar across the Asia-Pacific countries therefore, strategies to address these could be more effective if there were concerted efforts and joint resources amongst the countries.

Translational genomics and recent advances in oral squamous cell carcinoma.

Oral squamous cell carcinomas (OSCC) are a heterogeneous group of cancers arising from the mucosal lining of the oral cavity. A majority of these cancers are associated with lifestyle risk habits including smoking, excessive alcohol consumption and betel quid chewing. Cetuximab, targeting the epidermal growth factor receptor was approved for the treatment of OSCC in 2006, and remains the only molecular targeted therapy available for OSCC.