CTNNB1

点击蓝字 关注我们 编者按：近日，法国索邦大学Cordeliers研究中心Jean-Charles Nault教授研究团队在Gut杂志发表了一项最新临床研究成果，揭示了循环肿瘤DNA（ctDNA）在肝细胞癌（HCC）患者中的动态变化及其临床意义。该项研究为HCC的临床管理带来了新的视角和工具，ctDNA监测有望在未来成为HCC诊断和治疗的重要辅助手段。 文章发表封图 （ doi: 10.1136/gutjnl-2024-331956） 本研究通过深入分析来自173名HCC患者的772份血浆样本，以及56份作为对照的来自非HCC慢性肝病患者的血浆样本，旨在评估ctDNA作为一种有前景的非侵入性生物标志物在HCC患者中的动态变化及临床应用价值。 研究人员分别在三个时间点收集患者的血浆样本：诊断或治疗时（n=502）、局部区域治疗后24小时（n=154）以及随访期间（n=116）。此外，还收集了232份相应的肿瘤组织样本用于对比分析。 研究采用了先进的测序技术和数字PCR技术，对所有样本进行了游离DNA（cfDNA）浓度检测以及TERT启动子、CTNNB1、TP53、PIK3CA和NFE2L2等基因的突变分析。这些技术的结合使用，为研究者提供了高精度、高敏感度的检测结果。 结果显示，在活跃的HCC患者中，ctDNA的突变率高达40.2%，远高于非活跃的HCC患者的14.6%和无HCC对照组的1.8%（P<0.001）。进一步分析发现，TERT启动子的突变率最高，达到27.5%，其次是TP53（21.3%）和CTNNB1（13.1%），而PIK3CA和NFE2L2的突变率相对较低。值得注意的是，ctDNA中的突变大多与对应的肿瘤组织中的突变一致。 此外，研究还发现ctDNA的突变率随着肿瘤分期的进展而增加（P<0.001）。在103名接受经皮消融治疗的患者中，治疗前ctDNA中突变的存在和数量与更高的死亡风险（P=0.001）和复发率（P<0.001）显著相关。 有趣的是，局部区域治疗后24小时，cfDNA浓度和可检测的突变均有所增加。在53名接受系统治疗的患者中，基线时ctDNA的突变率为60.4%，且在接受atezolizumab-bevacizumab治疗的患者中，ctDNA中突变的持续存在与影像学上的疾病进展显著相关（63.6% vs 36.4%，P=0.019）。 Jean-Charles Nault教授表示，该项研究不仅证实了ctDNA作为HCC非侵入性生物标志物的潜力，还揭示了其在HCC监测、治疗反应评估和预后判断中的重要作用。通过对ctDNA的动态监测，医生可以更早地发现肿瘤复发或疾病进展的迹象，从而及时调整治疗方案。此外，ctDNA的检测结果还可以为个体化治疗提供指导，使治疗更加精准有效。 综上所述，本研究为HCC的临床管理带来了新的视角和工具，有望在未来成为HCC诊断和治疗的重要辅助手段。 原文链接：Campani C, Imbeaud S, Couchy G, et al. Circulating tumour DNA in patients with hepatocellular carcinoma across tumour stages and treatments. Gut Published Online First: 25 July 2024. doi: 10.1136/gutjnl-2024-331956 （来源：《国际肝病》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

10 scientists have been selected for OHC's first annual award to advance academic discoveries into clinical practice for rare diseases OXFORD, United Kingdom and CLEVELAND, Oct. 24, 2024 /PRNewswire/ -- The Oxford-Harrington Rare Disease Centre – a partnership between the University of Oxford, UK and Harrington Discovery Institute at University Hospitals, Cleveland, Ohio – today announces the first class of Oxford-Harrington Rare Disease Scholars. The scholar awards will support breakthrough treatments for rare and ultra-rare diseases across neurologic, oncologic, and metabolic disease areas, using small molecule, nucleic acid, viral, and cellular therapies. The recipients represent institutions across the UK, US, and Canada. The OHC brings together world-leading research, expertise in therapeutics development and new financial models to advance solutions to critical challenges in rare diseases. Each Scholar will receive £100,000 (UK) / $100,000 (US and Canada), personalised therapeutics development support from industry experts to help bring new therapeutics to market, and the opportunity to receive acceleration and investment funds of up to £1,000,000 based on project milestones. Matthew Wood, MD, PhD, Director and Chief Scientific Officer of the OHC, commented: "This first cohort of OHC Scholars is a testament to the outstanding quality of proposals we received from academics at institutions across the UK and North America. The breadth and standard of research into innovative approaches to treat rare diseases made our selection process very difficult, with successful proposals representing breakthrough discoveries defined by innovation, creativity and potential for clinical impact. Our congratulations go to the 2024 OHC Scholars and our sincere thanks go to all who submitted proposals – their continued efforts to make a meaningful difference for patients in need and their families are an inspiration to us all." Jonathan S. Stamler, MD, President of Harrington Discovery Institute, added: "By supporting each OHC Scholar with funding and an experienced therapeutics development team, we are maximising the potential of their discoveries to advance into the clinic. We have seen success with this approach at Harrington Discovery Institute and we are excited about replicating the model at the OHC. I look forward to seeing the progress of these innovative initiatives and sharing their advancements as the OHC continues to work towards providing scalable solutions to address the rare disease challenge globally." The 2024 OHC Rare Disease Scholar Award recipients, their organisations and fields of research are: Jacquelyn Bower, PhD – University of North Carolina at Chapel Hill, NC, USA Novel viral gene therapy to treat lethal rare eye tumours Louis Chesler, MD, PhD – Institute of Cancer Research, London, UK Regulatable cell therapies to treat brain cancers Charles Gersbach, PhD – Duke University, Durham, NC, USA Reprogramming immune cells for treatment of Hodgkin's lymphoma Xianxin Hua, MD, PhD – University of Pennsylvania, Philadelphia, PA, USA A new cellular strategy for treating acute myeloid leukaemia Michele Jacob, PhD – Tufts University School of Medicine, Medford, MA, USA A drug to treat brain abnormalities caused by CTNNB1 defects, an ultra-rare disease Bowen Li, PhD – University of Toronto, Toronto, Canada A nucleic acid therapy to treat cystic fibrosis, an inherited lung disease Michael Pacold, MD, PhD – New York University, New York City, NY, USA Drugs restoring brain function in rare metabolic diseases Carlo Rinaldi, MA, MD, PhD – University of Oxford, Oxford, UK Nucleic acid therapy for spinal and bulbar muscular atrophy (SBMA), a rare X-linked neuromuscular condition Timothy Yu, MD, PhD – Boston Children's Hospital, Boston, MA, USA Custom DNA-based therapy for a rare genetic disorder (PEX1 Zellweger Syndrome) Haiyan Zhou, MD, PhD – University College London, London, UK Nucleic acid therapy to treat loss of sensation and paralysis caused by a rare mutation For those interested in submitting a proposal for the Oxford-Harrington Rare Disease Scholar Award, the next funding call will open on the 15th of January 2025. For more information, visit: OxfordHarrington.org/funding/overview SOURCE Harrington Discovery Institute WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Oct. 10, 2024 -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, today announced an agreement with Roche to advance the evaluation of amezalpat (TPST-1120) in combination with atezolizumab (Tecentriq®) and bevacizumab, the current standard of care for unresectable or metastatic hepatocellular carcinoma (HCC), into a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic hepatocellular carcinoma, a form of liver cancer with high unmet need. Under the agreement, Roche will supply atezolizumab globally and Tempest will sponsor and lead the pivotal study. This agreement builds on a clinical collaboration between the companies pursuant to which amezalpat was combined with atezolizumab and bevacizumab in first-line HCC patients and compared to atezolizumab and bevacizumab alone in a randomized Phase 1b/2 study. Tempest retains all development and commercial rights to amezalpat. “We’re excited to announce this agreement that supports the advancement of amezalpat into a pivotal study and reinforces both Tempest and Roche’s shared commitment to delivering groundbreaking cancer treatments for patients,” said Stephen Brady, president and chief executive officer of Tempest. “Based on the positive Phase 2 data, I believe this combination therapy holds the potential to significantly improve first-line liver cancer treatment, and we look forward to amezalpat moving into this pivotal Phase 3 study.” In June, Tempest reported updated positive survival data from the ongoing global randomized Phase 1b/2 clinical study, demonstrating a six-month improvement in median overall survival (OS) for patients receiving the combination therapy, in comparison to the control arm of atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic HCC. The survival benefit observed in the amezalpat arm was maintained in key subpopulations, as well. These June data build upon previously released data from the primary analysis showing that the amezalpat combination therapy provided clinical benefit regardless of PD-L1 status and in patients with both immune excluded and immune desert tumors. Patients with a mutation in the beta catenin gene had an increased objective response rate and, in the updated data set, a longer median OS, both supported by amezalpat’s purported mechanism of action. In August, the company held its end-of-phase 2 meeting with the FDA where it reached broad agreement on the Phase 3 study plan, including the amezalpat dose schedule and primary endpoint of OS, which was a positive result from the Phase 2. The FDA also agreed on the statistical plan, including a pre-specified early efficacy analysis that the company currently estimates could shorten the study’s timeline to primary analysis by 8 months. The planned Phase 3 study is a global, blinded, 1:1 randomized study of amezalpat plus atezolizumab and bevacizumab vs. atezolizumab and bevacizumab, the standard of care, in patients with unresectable or metastatic HCC treated in the first line setting. In August 2024, the company received agreement from the FDA on its Phase 3 study design, dose of amezalpat, and the statistical plan, including a pre-specified efficacy analysis that could shorten the time to primary analysis. The company is preparing for the Phase 3 study start in the first quarter of 2025. Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggest that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In an ongoing global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the overall population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma. Tempest Therapeutics is a clinical-stage biotechnology company advancing a diverse portfolio of small molecule product candidates containing tumor-targeted and/or immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s novel programs range from early research to later-stage investigation in a randomized global study in first-line cancer patients. Tempest is headquartered in Brisbane, California. More information about Tempest can be found on the company’s website at www.tempesttx.com. The content above comes from the network. if any infringement, please contact us to modify.