Testicular Neoplasms

The largest study to date of most common form of testicular cancer has uncovered a possible link between disease risk and variations in the genes controlling cell shape and movement. By investigating the fundamental risk factors that may influence certain men inheriting testicular cancer, the study reveals new insights into how rare genetic variants may contribute to susceptibility – laying the groundwork for improved risk prediction and a better understanding of potential targets for future treatments. The study, led by researchers at The Institute of Cancer Research, London, compared the genetic data of men with and without testicular germ cell tumours (TGCTs). TGCTs are tumours formed in germ cells, which are the cells that develop into sperm in the testes and eggs in the ovaries. They represent the most common form of testicular cancer, accounting for more than 90 per cent of cases. This study, published in the journal European Urology Open Science, built on previous studies led by or involving scientists at The Institute of Cancer Research (ICR), analysed 1,435 TGCT cases and 18,284 cancer-free controls. The researchers used whole-exome sequencing – a technique for sequencing all the protein-coding regions of genes – to identify rare genetic variants that disrupt protein sequences and ultimately cause diseases, such as TGCTs. While previous genome-wide association (GWAS) studies have linked 78 fixed chromosome positions to TGCT risk – explaining more than 44 per cent of the disease’s heritability – much of the genetic basis remains unknown. To uncover additional genetic factors, the research team aimed to evaluate rare and disruptive mutations using models that explain how certain inherited characteristics, such as eye colour or health problems, are passed down in families. The study, which was primarily funded by the Movember Foundation and the ICR, which is both a research institute and a charity, pooled data from three TGCT case series, incorporating previous analyses conducted by the ICR and The Cancer Genome Atlas programme, as well as newly analysed cases from the UK Biobank. It also greatly benefitted from a newer and much larger dataset of cancer-free controls compared with prior studies, significantly improving its statistical prominence and reliability. This study reaffirms the understanding that TGCTs have a strong heritable basis (37–49 per cent), with immediate family members being four to six times more likely to develop the disease. While testicular cancer is highly treatable – with cure rates exceeding 95 per cent –better understanding how and why the disease runs in families could support earlier diagnosis and more targeted monitoring. Despite the team using the largest UK Biobank dataset to date, no individual genes were found to be significantly associated with TGCTs, highlighting the complexity of its genetic foundations and the need for continued research. This study emphasises the challenge of pinpointing rare genetic variants in driving TGCTs. While past research has pointed to possible genes such as DNAAF1 and CHEK2 playing a role in TGCT susceptibility, these associations have not been consistently confirmed in larger studies. The researchers did, however, through analysing groups of related genes, find that rare genetic variants potentially linked to TGCTs were found in genes associated with microtubular and ciliary pathways – the tiny structural and movement systems of cells that play a vital role in their function and development. These findings hint at multiple biological mechanisms that may contribute to TGCT development and warrant further investigation. First author Zeid Kuzbari, a PhD student in the Translational Genomics Group at the ICR, said: “While this study didn’t pinpoint a single causative gene, it has significantly advanced our understanding of TGCT genetics. The results suggest that testicular cancer risk is likely influenced by a complex interaction between multiple low-effect genetic variants rather than a single high-risk gene. “From a patient perspective, these findings reinforce the importance of genetic research and analysis in the early detection and risk assessment of testicular cancer in those patients at higher risk. Although we have yet to identify a definitive genetic marker for TGCTs, studies like this pave the way for more personalised approaches to cancer prevention and treatment.” The lack of replication in larger studies emphasises a key barrier in genetic research, termed the ‘Winner’s curse’, where initial findings are often difficult to confirm in larger studies performed later. With ongoing advancements in next-generation sequencing and data-sharing initiatives, future studies will continue to refine our understanding of TGCT genetics, ultimately leading to improved risk prediction and targeted interventions for those at a higher genetic risk. Senior author Professor Clare Turnbull, Professor of Translational Cancer Genetics in the Division of Genetics and Epidemiology and Group Leader of the Translational Genetics Group, said: “We are continuing our research efforts and are currently in the process of a much larger analysis involving samples from 8,000 men with TGCTs. Larger datasets and novel analytical approaches are crucial in driving both our understanding and identification of the factors contributing to TGCT susceptibility to ultimately improve patient outcomes in the years ahead.”

DUBLIN, Ireland and OXFORD, United Kingdom, April 14, 2025 (GLOBE NEWSWIRE) -- SynOx Therapeutics Limited (“SynOx”), a late-stage clinical biopharmaceutical company developing of emactuzumab for Tenosynovial Giant Cell Tumours (TGCT), today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to emactuzumab for the treatment of TGCT patients that are not amenable to or who would not benefit from surgery. Emactuzumab, a potentially best-in-class CSF-1 receptor (CSF-1R) inhibiting monoclonal antibody, is currently being evaluated in the TANGENT study, a global, multi-centre, randomized, double-blind, placebo-controlled registrational Phase 3 trial. TGCT is a rare, non-malignant but aggressively growing tumour of the synovium, tendon sheaths and bursa membranes primarily located in knee, hip, and ankle joints and caused by excessive production of CSF-1. It is a chronically debilitating disease for patients causing loss of function of the affected joints, as well as pain, stiffness and limited range of motion. Receipt of FTD for TGCT was supported by data from Phase 1/2 clinical studies demonstrating rapid, robust tumour reduction and durable response combined with a manageable safety profile. Emactuzumab has also previously received Orphan Medicinal Project designation from the European Medicines Agency. “The granting of FTD for emactuzumab in TGCT highlights the devastating toll that this disease has on patients, as well as the critical need that remains for new treatment options,” said Elyse Seltzer, M.D., Chief Medical Officer of SynOx Therapeutics. “Based on our clinical work to date, we believe that emactuzumab has significant potential to address key patient needs by offering an effective, short-course treatment with rapid onset and a durable response that allows individuals suffering from TGCT to better manage their disease and move forward with their lives. We look forward to completing the ongoing TANGENT study and progressing emactuzumab toward potential commercialization.” About Fast Track DesignationThe FDA grants Fast Track designation to facilitate the development and expedite the review of medicines to treat serious conditions and fill an unmet medical need. Fast Track status allows for enhanced communication and collaboration between the FDA and drug developers, potentially speeding up the delivery of life-saving treatments to patients. About Tenosynovial Giant Cell Tumour (TGCT)Tenosynovial Giant Cell Tumour (TGCT), previously termed pigmented villonodular synovitis (PVNS), is a type of tumour that affects the soft tissue lining of joints and tendons. TGCTs are categorised as fibrohistiocytic tumours by the WHO classification and are subclassified based on growth patterns (localised and diffuse types) and location (tendon sheath, intra- and extra-articular forms). TGCTs are locally destructive and can be aggressive. The disease causes significant joint pain, stiffness, loss of function and reduced quality of life. While most patients undergo surgery, more than 50% of those with diffuse TGCT experience tumour recurrence within three years. If left untreated, TGCT can cause joint deformity, degenerative changes, and even lead to arthrodesis or amputation in severe cases. About CSF-1 and EmactuzumabCSF-1 (or macrophage colony-stimulating factor) is a cytokine that binds to the CSF-1 receptor (CSF-1R), expressed on macrophages and other immune cells. Emactuzumab is a humanised IgG1 monoclonal antibody targeting CSF-1R, designed to inhibit and deplete macrophages in tumour tissue. Originally developed by Roche, emactuzumab has shown substantial efficacy in clinical studies in TGCT, including an objective response rate of ~71%, rapid tumour reduction, functional improvement, and good tolerability with a manageable safety profile. Emactuzumab may also have utility in other macrophage-driven diseases, and SynOx is actively exploring further development opportunities in these areas. Additional details regarding the ongoing registrational Phase 3 TANGENT study can be found on ClinicalTrials.gov (Identifier: NCT05417789). About SynOx TherapeuticsSynOx Therapeutics Limited is a Dublin and Oxford-based, late-stage clinical biopharmaceutical company developing emactuzumab, a best-in-class monoclonal antibody against CSF-1R, for the treatment of Tenosynovial Giant Cell Tumour (TGCT) and other CSF-1-related and macrophage-driven disorders. SynOx is led by an experienced team of industry professionals with a successful track record of developing and bringing products to commercialization. The company is backed by a strong syndicate of premier life science investors including Forbion, Gilde Healthcare, HealthCap, Bioqube Ventures and Medicxi. Contacts: SynOx Therapeutics Ray Barlow Chief Executive Officer Tel: +44 (0) 208 058 5619 Email: enquiries@synoxtherapeutics.com Vida Strategic Partners (on behalf of SynOx) Tim Brons (Media) 415-675-7402 tbrons@vidasp.com

DETROIT, April 7, 2025 /PRNewswire/ -- The Barbara Ann Karmanos Cancer Institute, cancer centers, and other organizations nationwide recognize April as Testicular Cancer Awareness Month. This cancer occurs when cells grow out of control in the testicles, part of the male reproductive system, and there are multiple forms of testicular cancer. Testicular Cancer Facts and Figures According to the American Cancer Society (ACS): Continue Reading Young adult males talking in a park. GettyImages/Thurtell In 2025, about 9,720 new testicular cancer cases will be diagnosed. About one of every 250 males will develop testicular cancer at some point in their lives. This cancer can affect young males, with the average age at the time of diagnosis being 33. About 6% of cases occur in children and teens, and about 8% occur in men over 55. Because testicular cancer can usually be treated successfully, a man's lifetime risk of dying from this cancer is about 1 in 5,000. Testicular Cancer Symptoms and Risk Factors While some testicular cancer cases have no signs or symptoms, signs of this disease can often be caught during a routine exam. "With the absence of symptoms in the early stages of testicular cancer, I continue to stress the importance of males getting their annual wellness checks with their primary care providers and not hesitating to see their providers if something is not normal," expressed Nitin Vaishampayan, M.D., radiation oncologist and leader of the Genitourinary Oncology Multidisciplinary Team (MDT) at Karmanos. Symptoms may include swelling of the testicle, a lump, a feeling of heaviness or pain in the scrotum, and aches in the lower abdomen. In rare cases, breast growth or soreness may occur. Certain testicular tumors may cause early puberty in boys. Many men who develop testicular cancer do not have any risk factors. However, the following may cause a higher risk of the disease: An HIV infection. An undescended testicle. Being of a certain race or ethnicity – White men are four to five times more likely to develop testicular cancer. Americans and Europeans have the highest risk. Family history of testicular cancer or having had testicular cancer before. Testicular Cancer Treatment at Karmanos Cancer Institute At Karmanos, testicular cancer is treated by the Genitourinary Oncology MDT, which includes surgical oncologists, medical oncologists, radiation oncologists, radiologists, pathologists, pharmacists, nurse practitioners, dietitians, social workers, and genetic counselors. The team focuses entirely on treating genitourinary cancers and shares its collective expertise to create a customized treatment plan for each patient. The team uses the latest technologies, including the da Vinci® Xi™ Surgical System and cryotherapy, to achieve optimum patient success. To learn more, visit karmanos.org. About the Barbara Ann Karmanos Cancer Institute Karmanos Cancer Institute is a leader in transformative cancer care, research and education through courage, commitment and compassion. The Karmanos vision is a world free of cancer. As part of McLaren Health Care, Karmanos is the largest provider of cancer care and research in Michigan. For more than 75 years, the administrative and research headquarters, along with the premier specialty cancer hospital, have been located in downtown Detroit. With 17 network sites, Karmanos delivers world-renowned care and access to clinical trials throughout Michigan and northern Ohio. The National Cancer Institute recognizes Karmanos as one of the best cancer centers in the nation with a comprehensive cancer center designation. Its academic partnership with the Wayne State University School of Medicine provides the framework for cancer research and education – defining new standards of care and improving survivorship. For more information, call 1-800-KARMANOS (800-527-6266) or visit karmanos.org. Follow Karmanos on Facebook, Twitter, LinkedIn and YouTube. SOURCE Karmanos Cancer Institute WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED