Researchers discover urine-based test to detect head and neck cancer

Source: Author: Michigan Medicine - University of Michigan Researchers from the University of Michigan Health Rogel Cancer Center have created a urine-based test that detects pieces of DNA fragments released by head and neck tumors. The test could potentially facilitate early detection of this cancer type, which currently does not have a reliable screening method. Human papillomavirus (HPV) is widely recognized for causing cervical cancer, but is increasingly found to cause cancers in the mouth, throat and other head and neck regions. Early detection is critical because detecting a cancer at an earlier stage can lead to better outcomes for patients. Using whole genome sequencing, the Rogel group showed that cell-free DNA fragments released by tumor cells, which are passed on from the bloodstream into urine through the kidneys, are predominantly ultra-short, with fewer than 50 base pairs. Given their small size, these fragments are likely to be missed using conventional urine or blood-based liquid biopsy tests in detecting circulating tumor DNA (ctDNA). The research was led by Muneesh Tewari, M.D., Ph.D., professor of hematology and oncology, J. Chad Brenner, Ph.D., associate professor of otolaryngology-head and neck surgery, and Paul L. Swiecicki, M.D., associate medical director for the Oncology Clinical Trials Support Unit at Rogel. Initial results are published in JCI Insight. “In this study we provide evidence to support the hypothesis that conventional assays do not detect ultrashort fragments found in urine, since they are designed to target longer DNA fragments. Our team used an unconventional approach to [...]

Insilico Medicine’s AI-driven approach yields promising PTPN2/N1 inhibitor for cancer immunotherapy

Source: Author: InSilico Medicine staff In recent years, cancer immunotherapy, exemplified by PD-1 and its ligand PD-L1 blockade, has made remarkable advances. But while immunotherapy drugs offer new treatment possibilities, only about 20% to 40% of patients respond to these treatments. The majority either don't respond or develop drug resistance. Researchers are now looking for ways to enhance the scope of tumor immunotherapy in order to benefit a wider range of patients. One such avenue is through the protein tyrosine phosphatase non-receptor type 2 (PTPN2) and its close superfamily member, PTPN1, identified in previous research as crucial modulators involved in the regulation of immune cells signaling pathways that promote tumorigenesis by attenuating tumor-directed immunity. While promising, the development of PTPN2/PTPN1 inhibitors has faced challenges as a result of unfavorable pharmacokinetics due to the highly cationic active site and the relatively shallow nature of the protein surface. In a significant milestone, researchers at Abbvie discovered the dual PTPN2/N1 inhibitor ABBV-CLS-484 through structure-based drug design and optimization of drug-like properties. Now, clinical stage artificial intelligence (AI)-driven drug discovery company Insilico Medicine ("Insilico") has initiated a program with a fast-follow strategy to design a novel PTPN2/N1 inhibitor with drug-likeness properties and in vivo oral absorption, supported by the Company's generative AI drug design engine Chemistry42. The research was published in the European Journal of Medicinal Chemistry on April 5. Scientists inputted the structure of the known PTPN2/N1 inhibitor as a reference compound to Chemistry42 as a starting point and generated a series [...]

The growing role for cfHPV-DNA testing in OPSCC therapeutic development

Source: Author: Sysmex Inostics,sponsored content Human papillomavirus (HPV) plays a key role in the development of oropharyngeal squamous cell carcinoma (OPSCC). Approximately 80% of all OPSCC cases in the U.S. are associated with HPV.1 In fact, the incidence of HPV-associated OPSCC in men has surpassed that of cervical cancer in women, making OPSCC the most common cancer caused by HPV in the U.S.2 As pharmaceutical companies seek to develop targeted therapeutics for HPV-associated cancers, access to robust biomarkers can prove invaluable for drug development. cfHPV-DNA in plasma meets this need and represents an attractive biomarker for grading treatment response and recurrence surveillance. Here, we’ll discuss the growing role for cfHPV-DNA as a biomarker in developing novel therapeutics targeting HPV-associated OPSCC and how HPV-SEQ — a quantitative, ultrasensitive test for cfHPV-DNA — can be leveraged during development for such therapies. The rise of cfHPV-DNA as a biomarker for HPV-associated OPSCC It has long been known that HPV-associated oropharyngeal cancers shed HPV-DNA into the circulatory system. However, drug developers now have an opportunity to not only detect but also quantify cfHPV-DNA in plasma to assess the effectiveness of therapeutics during development. “With real-time insights, you can get a very keen sense of how the tumor is responding to intervention during a clinical trial, including de-escalation clinical trials,” explained Nishant Agrawal, MD, co-director, head and neck surgical oncology at University of Chicago Medicine. “In the past, measuring responses has taken months or even years. But with cfHPV-DNA testing, you can do it [...]

‘Paradoxical’ data show routine imaging lacks benefit for head and neck cancer survivors

Source: Author: Matthew Shinkle Key takeaways: Researchers saw no statistical difference between patient groups with respect to treatment outcomes. Larger studies are needed to further evaluate this study’s findings. Compared with expectant management, imaging-based surveillance did not improve outcomes among patients in remission after completion of primary radiation therapy for head and neck cancer, according to data published in JAMA Network Open. Although imaging “in the context of clinical suspicion” for this specific patient population is common and typically beneficial, according to researchers, the results of this study show that such a practice is not valuable for asymptomatic patients. “The results of the present study, while seemingly paradoxical, are consistent with those of others which have failed to demonstrate a benefit to surveillance imaging among patients who have successfully completed treatment for head and neck cancer,” Allen M. Chen, MD, MBA, professor and chair of the department of radiation oncology at University of California, Irvine, Chao Family Comprehensive Cancer Center, and researchers wrote. Researchers conducted a retrospective, comparative effectiveness review to evaluate the potential benefit of surveillance imaging among asymptomatic patients with head and neck cancer currently in remission following completion of chemoradiation. The study included 340 adults (59% men; 43% white) who had achieved a complete metabolic response to initial treatment for newly diagnosed squamous cell carcinoma of the head and neck between January 2014 and June 2022. Researchers defined surveillance imaging as the acquisition of a PET with CT, MRI or CT of the head and neck [...]

CERN detector could help treat brain tumors with greater precision

Source: Author: Ashwini Sakharkar Mária Martišíková (left), the project leader from Heidelberg University Hospital and German Cancer Research Center (DKFZ), and DKFZ researcher Laurent Kelleter. Credit: Heidelberg University Hospital / H.Schroeder Scientists are testing a new device that will help them more accurately target cancer cells during ion radiotherapy for head and neck tumors. Scientists from the German National Center for Tumor Diseases (NCT), the German Cancer Research Center (DKFZ), and the Heidelberg Ion Beam Therapy Center (HIT) at Heidelberg University Hospital are currently testing the imaging device on their first patients. The device includes a small Timepix3 pixel detector developed at CERN, which allows head and neck tumors to be closely monitored during ion radiotherapy, making them easier to target and thus helping limit the treatment’s side effects. “One of the most advanced methods for treating head and neck tumors involves irradiation with ion beams. This has one unique feature: it can be precisely tailored to the depth inside the human head where the particles should have the maximal effect”, explains Mária Martišíková, the head of the DKFZ team. Like other forms of irradiation, ion radiation can have drawbacks. While it can be effective in targeting tumors, it can also affect healthy tissue surrounding the tumor. In the case of brain tumors, this can be particularly challenging, as damage to the optic nerve or a patient’s memory is possible. Ideally, the irradiated area around the tumor should be minimized while maximizing the dose to the tumor. [...]

Rhod Gilbert: Doctor reveals how ‘brutal’ therapy tackled comedian’s cancer

Source: Author: Natalie Grice, BBC News Prof Mererid Evans says Rhod Gilbert "wanted something positive to come out of his experience" "A patient once described it to me as brutal, and it's really stuck with me, because it's difficult to go through." What's so brutal? It's the cancer treatment Prof Mererid Evans routinely prescribes to the people who come to her, hoping she will save their lives, and which she aims to improve with research she is leading. It was the same word used by Welsh comedian Rhod Gilbert when in 2022 he found himself sitting in front of the consultant oncologist after being diagnosed with throat, neck, tongue and tonsil cancer. Rhod Gilbert was a patron of Velindre Cancer Centre for 10 years before his diagnosis Her famous patient suddenly put her consulting room at Velindre Cancer Centre, Cardiff, in the limelight when he made a documentary about his treatment. "Rhod wanted something positive to come out of his experience," said Prof Evans, 54, head and neck specialist at Velindre Cancer Centre in Cardiff, a professor at Cardiff University's cancer and genetics division, and head of the Wales Cancer Research Centre. "We talked about the treatment he'd be receiving and I think he felt it was an opportunity to highlight what it's like going through cancer treatment." The resulting Channel 4 programme, A Pain in the Neck for SU2C, followed Gilbert through diagnosis, treatment and the aftermath. Head and neck cancer is the eighth [...]

A case for radiation enhancement in head and neck cancer

Source: Author: M. Alexander Otto, PA, MMS Two new exploratory studies of radioenhancers used in combination with radiation therapy in the treatment of head and neck cancers showed that these agents can boost the effectiveness of radiotherapy in these cancers. The two phase 2 studies, presented at the 2024 American Society for Radiation Oncology (ASTRO) Head and Neck Cancer Symposium on March 1, 2024, found an increase in 1-year local control rate, progression-free survival, and overall survival. In one study, which explored the use of the hedgehog pathway inhibitor vismodegib alongside radiation therapy, researchers found that all but one patient with locally advanced, unresectable basal cell carcinoma (BCC) demonstrated 1-year local control — a significantly better rate than that expected from radiation alone — and 83% were alive at 5 years. The second, which explored the use of hafnium oxide nanoparticles (NBTXR3) prior to radiation therapy, also reported promising results. Patients with T3/4 locally advanced head and neck squamous cell carcinoma of the oropharynx or oral cavity who were ineligible for chemoradiation demonstrated a median overall survival of 18.1 months vs 12 months, the life expectancy with radiation alone. Although small, both studies suggest a role for radioenhancers in head and neck cancer, Jonathan Schoenfeld, MD, a head and neck cancer radiation oncologist at the Dana Farber Cancer Institute, in Boston, Massachusetts, told Medscape Medical News.

Prognostic factors linked with poor locoregional control in tongue cancer

Source: Author: Gina Mauro Depth of invasion, lymphovascular space invasion, and positive glossectomy specimen margins were all found to be linked with inferior locoregional control (LRC) in patients with pT1-2N0 oral tongue squamous cell carcinoma who were treated with partial glossectomy and elective neck dissection alone. The retrospective findings, which were presented during the 2024 ASTRO Multidisciplinary Head and Neck Cancers Symposium, were seen even with final negative tumor bed margins. Results showed that, at a median follow-up of 45.6 months, the 3-year LRC and overall survival (OS) rates were 88.0% and 92.5%, respectively, in the all-comer patient population. In patients with pT1 disease, these rates were 92.0% and 95.2%, respectively; they were 85.0% and 90.5% in those with pT2 disease. However, upon the multivariate analysis, those with positive glossectomy margins had worse LRC (HR, 6.66; 95% CI, 1.60-27.78; P = .009). Lymphovascular space invasion (HR, 6.90; 95% CI, 1.42-33.65; P = .02) and depth of invasion (HR, 1.31; 95% CI, 1.06-1.63; P = .01) were also associated with inferior LRC. “Patients with these risk factors may be considered for adjuvant radiotherapy to optimize disease control,” lead study author Michael Modzelewski, MD, of Kaiser Permanente Bernard J. Tyson School of Medicine, in Pasadena, California, and coinvestigators wrote in a poster presented at the meeting. Patients who have early-stage tongue squamous cell carcinoma do not typically receive adjuvant radiation because they are often at low risk for recurrence. Following surgery, the status of main glossectomy specimen margin has been shown [...]

Novel therapy promising for radiation-induced oral mucositis

Source: Author: Mike Bassett, Staff Writer, MedPage Today The first-in-class uridine phosphorylase inhibitor TK-90 almost completely eliminated severe oral mucositis (SOM) in patients with non-metastatic squamous cell carcinoma of the head and neck who underwent radiation therapy, a small randomized study showed. None of the 12 patients treated with TK-90 developed SOM by the end of treatment at week 7, compared with six of 12 treated with placebo (0% vs 50%, P=0.14), reported Nabil F. Saba, MD, of the Winship Cancer Institute of Emory University in Atlanta. At week 9 follow-up after the end of dosing, just one patient treated with TK-90 had developed SOM compared with nine in the placebo group (8.3% vs 75%, P=0.003). The duration of SOM in the patient treated with TK-90 was 12 days compared with a mean duration of 35 days in patients who developed SOM in the placebo arm (P=0.026). "Parenteral administration of TK-90 appears to be an effective strategy for preventing radiation-induced mucositis," Saba said during a session at the Multidisciplinary Head and Neck Cancers Symposiumopens in a new tab or window in Phoenix. "These results merit additional validation in larger trials." Mucositis is a debilitating complication of radiotherapy or chemotherapy, leading to weight loss, mouth ulcers, abdominal pain, vomiting, diarrhea, and potentially fatal infections. "Uridine is essential to the preservation of the health of the normal mucosa," Saba explained. "By inhibiting uridine phosphorylase, uridine levels are restored in the mucosa, basically reducing the leakage in the mitochondria and, by doing [...]

Case Western Reserve University-led research team discovers new method to test for oral cancer

Source: Author: staff Oral cancers and precancerous mouth lesions are considered especially difficult to diagnose early and accurately. For one, biopsies are expensive, invasive, stressful for the patient and can lead to complications. They’re also not feasible if repeated screenings of the same lesion are required. But a team of researchers, led by a clinician scientist at Case Western Reserve University School of Dental Medicine, has discovered a noninvasive, low-cost test to detect oral cancer, monitor precancerous lesions and determine when a biopsy is warranted. Their findings, published online March 4 in the journal Cell Reports Medicine are based on a scoring system linked to the levels of two proteins in cells brushed from suspicious oral lesions of patients at dental clinics or the ear, nose and throat department at University Hospitals (UH). One of the proteins (human beta defensin 3 or hBD-3) is expressed at high levels in early-stage oral cancer, while the second (hBD-2) is low or unchanged. The ratio of hBD-3 to hBD-2 in the lesion site—over the ratio of the two proteins on the opposite, normal site—generates a score, called the beta defensin index (BDI). A score above a predetermined threshold implies cancer; anything below does not. Determining the levels of the proteins and quantifying the BDI is done routinely in a lab. The BDI was independently validated using identical protocols at CWRU/UH, University of Cincinnati Medical Center and West Virginia University School of Dentistry. Aaron Weinberg “When we first discovered hBD-3, we saw it [...]

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