Using proteogenomics to improve the treatment of squamous cell carcinoma

Source: blogs.bcm.edu, Baylor College of Medicine Author: Molly Chiu Patients with head and neck squamous cell carcinoma (HNSCC), the sixth most common epithelial cancer worldwide, are treated with surgery, chemotherapy and radiotherapy. In addition, targeted agents, including an EGFR monoclonal antibody (mAb) inhibitor and two programmed cell death protein 1 (PD-1) inhibitors, have been approved by the U.S. Food and Drug Administration for HNSCC treatment, but response rates are moderate. In this study, researchers led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated what new insight proteogenomic analysis might offer into understanding why certain patients respond to certain treatments while other patients do not. They propose that their findings may help better match patients to an appropriate course of treatment in the future. Building a proteogenomic profile The team profiled proteins, phosphosites (a site on a protein associated with phosphorylation) and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies. “We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be a good candidate for a different type of therapy – EGFR inhibitors, CDK inhibitors or immunotherapy,” said Dr. Bing Zhang, lead contact of the study and professor in the Lester and Sue Smith Breast Center and the Department of Molecular and Human Genetics at Baylor. “We also identified candidate biomarkers that could be used to match patients to effective [...]

2021-02-04T21:09:30-07:00February, 2021|Oral Cancer News|

Deciphering molecular intelligence for early oral cancer detection

Source: www.openaccessgovernment.org Author: Muy-Teck Teh, Senior Lecturer, Queen Mary University of London Muy-Teck Teh, Senior Lecturer from Barts and the London School of Medicine & Dentistry, Queen Mary University of London discusses how a novel low-cost rapid digital diagnostic test could help save lives and reduce head and neck cancer burden worldwide: Head and neck squamous cell carcinoma (HNSCC) is a heterogenous group of diseases involving malignancies of the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses and salivary glands. It is the sixth most common cancer, with an incidence of around 600,000 cases worldwide. These numbers are expected to double by 2035, according to the World Health Organization (WHO). Despite advances in treatment options for oral cancer (mostly oral squamous cell carcinoma, OSCC), the 5-year survival rate (~50%) has not improved over the last half century, mainly because many malignancies are not diagnosed until late stages of the disease. Published data showed that over 70% of OSCC patients have some form of pre-existing oral premalignant disorder (OPMD) lesions amenable to early diagnosis and risk stratification. Hence, the potential to reduce the morbidity and mortality of OSCC through early detection is of critical importance. Century old diagnostic method needs upgrading OPMDs are very common but clinicians are unable to differentiate between high- and low-risk OPMDs through histopathological gold standard method based on subjective opinion provided by pathologists. As there is currently no quantitative method to detect high-risk lesions, most OPMD patients are indiscriminately put on time consuming, costly and stressful [...]

2020-11-15T09:08:56-07:00November, 2020|Oral Cancer News|

Blood marker may reduce cancer burden: Progress with microRNA biomarker

Source: www.eurekalert.org Author: Flinders University Researchers at Flinders University are expanding work on a promising blood test model to help predict or diagnose head and neck cancer, a difficult cancer to pick up early and treat. With cancer accounting for almost 10 million a year, the Global Burden of Disease report (2017) attributed more than 380,000 deaths to head and neck cancer. The Australian research at Flinders University has discovered a blood serum microRNA biomarker signature for oropharyngeal squamous cell carcinoma, recently reported in a new study in the Journal of Translational Medicine (BMC Springer Nature). The signature might have potential for the detection of other squamous mucosal Head and Neck cancers, the researchers say, adding the latest development, flowing from previous NHMRC Australian Government funding for developing blood biomarkers for oesophageal cancer, is encouraging. "MicroRNAs are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers," says Flinders University researcher Dr Damian Hussey. "If our test can be translated to clinic, then it could facilitate surveillance, earlier diagnosis and treatment - including for identifying people with early stage, or at increased risk of developing, Head and Neck cancer," says fellow researcher Associate Professor Eng Ooi. The latest study used a novel approach to produce a biomarker signature with good cross validated predictive capacity. Researchers say the results warrant further [...]

2020-09-01T18:20:29-07:00September, 2020|Oral Cancer News|

Accurately identifying aggressive head and neck cancers

Source: www.eurekalert.org Author: press release The Case Western Reserve-led research team will analyze computerized images of tissue samples for patterns which could become "biomarkers," or predictors, for determining relative risk for recurrence in one particularly common type of head and neck cancers. Those tumors, known as oropharyngeal cancers, occur primarily at the base of the tongue and in the tonsils. Currently, however, oncologists tend to treat all of these tumors with the same aggressive level of therapy. This is the case even though many of the oropharyngeal tumors which are caused by the human papilloma virus (HPV) tend to have favorable outcome-regardless of treatment-while another subset of the tumors progress and metastasize, or spread. "Right now, it's a one-size-fits-all therapy for all of these patients with HPV head and neck cancers," said Anant Madabhushi, MD, the F. Alex Nason Professor II of Biomedical Engineering, founding director of the CCIPD at the Case School of Engineering and primary investigator in the new research. "There are currently very few validated biomarkers and approaches that are accurate enough to be able to identify which of these cancers are more aggressive or which ones are less aggressive," he said. "That has limited the ability of clinicians to even hold clinical trials to find out if they can de-escalate therapy for some of these patients-or who needs more aggressive therapy." The National Cancer Institute (NCI) recently awarded a $3.15 million, five-year academic-industry partnership grant to Madabhushi and his team to pursue the research and build [...]

Predicting throat cancer recurrence with a blood test

Source: knowridge.com Author: from University of Michigan Health System A new study suggests the possibility of predicting at its earliest stages when a type of head and neck cancer will come back. Oropharyngeal cancer — which occurs in the throat, tonsils and back of the tongue — is frequently linked to the human papilloma virus. That’s good news, in a way, as HPV-related cancers are generally more responsive to treatment. But for about 15 to 20 percent of these patients, the treatment won’t work and their cancer will return. There are no known biomarkers to predict when treatments are likely to fail. In a new study in Clinical Cancer Research, researchers found that patients whose oropharyngeal cancer recurred had higher levels of antibodies for two proteins, E6 and E7, which are found in HPV-fueled cancers. The finding suggests a potential blood-based marker that could predict when cancer is likely to return. For this study, researchers looked back at 52 patients with advanced oropharyngeal cancer who had enrolled in a prior study: 22 who had developed recurrence and 30 who had not. The two groups were similar in age, cancer classification and smoking status. All tumors were linked to the human papilloma virus. On average, cancer recurred 13 months after a patient’s treatment ended. Serum was measured via a blood test at diagnosis or start of treatment, then repeated after treatment ended and about every three months after. Initially, there was no difference in E6 and E7 antibody levels between those [...]

2016-12-17T10:55:56-07:00December, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com Author: Laura Panjwani Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD. “Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.” The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN. The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator's choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act. Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN. OncLive: What [...]

2016-08-24T13:28:58-07:00August, 2016|Oral Cancer News|

Cancer gene may aid researchers find how immune system can help treat cancer or predict outcomes

Source: immuno-oncologynews.com Author: Daniela Semedo, PhD University of Cincinnati scientists have recently discovered that DEK, a human gene known to cause cancer, can be detected in the plasma of patients with head and neck cancer. DEK may help clinicians understand how a person’s immune system can be used to treat cancer or predict outcomes for patients. The information, titled “The DEK oncogene can be detected in the plasma of head and neck cancer patients and may predict immune response and prognosis,” was presented via poster at the Multidisciplinary Head and Neck Cancer Symposium Feb. 18-20 in Scottsdale, Arizona. “Head and neck cancer remains the sixth most common cancer worldwide,” said Trisha Wise-Draper, M.D., Ph.D., assistant professor in the Division of Hematology Oncology at the UC College of Medicine, in a news release. Wise-Draper is a member of both the Cincinnati Cancer Center and UC Cancer Institute and she was the principal investigator on this study. “Although infection with the human papilloma virus, or HPV, has emerged as a factor for determining outcomes for head and neck squamous cell carcinoma [head and neck cancer], leading to less intense treatment strategies for patients, no plasma biomarkers exist to predict tumor response to treatment or possible relapse,” she said. “One potential plasma biomarker is programmed by the human DEK gene, which has been found to promote cancer. DEK RNA and protein are highly increased in tissue specimens from several tumor types, including head and neck cancer, breast cancer, and melanoma, and antibodies to [...]

HPV Persistence Predicts Poor Prognosis in Head/Neck Cancer

Source: www.medscape.comAuthor: Roxanne Nelson, RN, BSN Among patients with human papillomavirus–positive oropharyngeal cancer (HPV-OPC), persistence of HPV following treatment is associated with a poorer prognosis. Results of a new study show that the persistence of HPV16 DNA, detected in oral rinses after treatment has ended, may be predictive of disease recurrence. In a cohort of 124 patients with HPV-OPC, HPV16 DNA was detected in oral rinses from 54% (n = 67) of patients at the time of their diagnosis. Following treatment, it was detected in only six patients after treatment, including five patients with persistent oral HPV16 DNA that was also detected at diagnosis. All five patients with persistent HPV16 experienced disease recurrence, with three eventually dying of their cancer. Conversely, only nine of 119 patients without persistent oral HPV16 DNA developed recurrent disease. "Our findings indicate that persistent HPV16 DNA in oral rinses may be a useful early marker of disease that has either recurred or never fully responded to treatment," said first author Eleni Rettig, MD, of the Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. "In the clinical setting, this could one day be a part of routine surveillance after treatment for HPV-positive oropharyngeal cancers, in addition to clinical examination and imaging," she told Medscape Medical News. The study was published online July 30 in JAMA Oncology. Biomarker Potential? In an accompanying editorial, Julie E. Bauman, MD, MPH, and Robert L. Ferris, MD, PhD, both of the University of Pittsburgh, in Pennsylvania, [...]

Five game changers: will they alter the course of dental hygiene treatment?

Source: www.rdhmag.com Author: Karen Davis, RDH, BSDH With the beginning of a new year, clinicians may be wondering what new technologies or services they should consider. As I reflected on this, it led me to consider what has the potential to become game changers for dental hygienists. I immediately considered the integration of laser technology, sharpen-free instruments, ergonomic operator chairs, CAMBRA, adjunctive devices for caries detection, and oral cancer screenings. Within minutes, I had a list of about 25 technologies and services that have completely altered how I practice dental hygiene from the day I started in 1979. So I decided to feature a few technologies I believe are underutilized or, in a few cases, even unknown by clinicians who have the potential to substantially alter patient care. Automated and unassisted periodontal charting In the world of dental hygiene, having another person enter data into the computer or record periodontal data is either a luxury or is uncommon. Dental hygienists everywhere seem caught in the time trap of laboriously entering the data or, in many cases, settling for spot probing and incomplete data collection. But automated technologies to collect and enter the data unassisted have been available to dental hygienists for decades, and when integrated, have the potential to help diagnose periodontal diseases in the earliest possible stages. Dental R.A.T. (Remote Assisted Technology) is a foot-operated device that enables the clinician to enter periodontal data unassisted using hand-eye-foot coordination. It integrates to major software programs, automatically entering the data into [...]

Proteomic analysis of oral/head and neck cancer

Source: http://cancerres.aacrjournals.orgAuthor: Shen Hu, Lifeng Zhang, Jiang Jiang, Martha Arellano-Garcia, and David Wong Abstract: The stagnant survival rates over the past few decades for patients with oral/head and neck squamous cell carcinoma (OSCC/HNSCC) emphasize the need for identifying novel diagnostic and therapeutic targets based on molecular profiling of the tumor. In this study, we have conducted patient-based proteomic analysis towards the discovery of potential serum and tissue protein targets associated with OSCC/HNSCC. First, we have utilized quantitative proteomics based on gel electrophoresis and stable isotope labeling/tandem mass spectrometry (MS/MS) to identify differentially expressed serum proteins between lymph-node metastatic and non-metastatic OSCCs. Proteins in PAGE gel bands were digested and the resulting peptides were labeled with iTRAQ reagents and subsequently quantified with liquid chromatography (LC) with quadrupole time-of-flight MS or linear ion trap MS (LTQ). The differentially expressed proteins included transthyretin, alpha-fibrinogen, tetranectin, hemopexin, ficolin, HGF activator, plasminogen, clusterin, etc. Second, we have performed comparative proteomic analysis of human papillomavirus (HPV)-positive and HPV-negative HNSCCs because HPV has been recognized as an important risk factor for a subset of OSCC/HNSCC. Differentially expressed proteins were revealed by 2-D gel electrophoresis and then identified using in-gel tryptic digestion followed by LC-MS/MS (linear ion trap). Interesting targets associated with HPV-positive HNSCC included NHEJ1, PARK7 (oncogene DJ-1), superoxide dismutase, heat shock protein beta-1, fatty acid-binding protein, etc. NHEJ1 is a DNA repair protein involved in DNA nonhomologous end joining whereas PARK7 acts as a positive regulator of androgen receptor-dependent transcription and has cell-growth promoting and transforming activities. In addition, [...]

2014-10-10T11:26:28-07:00October, 2014|Oral Cancer News|
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