撰文丨王聪 编辑丨王多鱼 排版丨水成文 对于无法切除或晚期的 肝细胞癌 （HCC） 患者而言，全身系统性治疗是最佳选择。然而，其疗效受到耐药性的限制。 铁死亡 （ ferroptosis ） 是一种独特的受控细胞死亡形式，在肝细胞癌 （HCC） 的全身系统性治疗中发挥着至关重要的作用。 2025 年 10 月 27 日， 海军军医大学免疫与炎症全国重点实验室 邹最 教授、 于益芝 教授、 徐胜 教授等 ， 在 Nature 子刊 Nature Cancer 上发表了题为： SCRN1 confers hepatocellular carcinoma resistance to ferroptosis by stabilizing GPX4 via STK38-mediated phosphorylation 的研究论文。 该研究表明， SCRN1 通过 STK38 介导的磷酸化稳定 GPX4 ，从而赋予 肝细胞癌 （HCC） 对 铁死亡 的抵抗，从而 为肝细胞癌 （HCC） 的治疗提供了潜在 靶点和策略。 在这项最新研究中，研究团队发现， SCRN1 蛋白与 肝细胞癌 （HCC） 的 铁死亡抵抗 及 不良预后 ...

Core Viewpoint - The company has completed the first patient dosing in a Phase II clinical trial evaluating the combination of Tinengotinib with Kanfang Biotech's anti-cancer drugs for advanced hepatocellular carcinoma [1][2] Group 1: Clinical Trial Details - The trial is an open-label, multicenter Phase II study conducted in China, aimed at assessing the efficacy and safety of Tinengotinib in combination with Kanfang's drugs, Kadyuoni (PD-1/CTLA-4) and Yidafang (PD-1/VEGF) [2] - The primary objective of the trial is to evaluate the safety and effectiveness of the combination therapies compared to Tinengotinib monotherapy in patients with advanced hepatocellular carcinoma who have not received prior systemic anti-tumor treatment or have failed standard treatment [2] Group 2: Collaboration and Development - The company has established a collaboration agreement with Kanfang Biotech to jointly develop clinical combination therapies in the field of hepatocellular carcinoma [2]

Core Viewpoint - The company announced the initiation of a Phase II clinical trial for its core product, Tinengotinib (TT-00420), in combination with other therapies for the treatment of advanced hepatocellular carcinoma (HCC) [1] Group 1: Clinical Trial Details - The trial is an open-label, multicenter Phase II study conducted in China [1] - The primary objective is to evaluate the safety and efficacy of Tinengotinib in combination with Kanfar Biotech's Katanib (PD-1/CTLA-4) and Yida Pharma's Yivofisi (PD-1/VEGF) [1] - The target population includes patients with advanced HCC who have not previously received systemic anti-tumor therapy or have failed standard treatment [1] Group 2: Collaboration and Development - The company has entered into a collaboration agreement with Kanfar Biotech to jointly develop clinical combination therapies in the field of hepatocellular carcinoma [1]

Core Insights - Tempest Therapeutics has received approval from the National Medical Products Administration (NMPA) in China to initiate a pivotal trial for amezalpat (TPST-1120) in combination with atezolizumab and bevacizumab for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC) [1][2][3] Company Overview - Tempest Therapeutics is a clinical-stage biotechnology company focused on developing targeted and immune-mediated therapeutics for cancer treatment [8] - The company is headquartered in Brisbane, California, and has a diverse portfolio of small molecule product candidates [8] Drug Development - Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist that shows promise in treating cancer by targeting tumor cells and modulating the tumor microenvironment [7] - The planned Phase 3 study will be a global, blinded, 1:1 randomized trial comparing amezalpat plus atezolizumab and bevacizumab against a placebo combination for first-line treatment of HCC [3] - The company has received agreement from both the FDA and EMA on the study design and statistical plan for the Phase 3 trial [3] Hepatocellular Carcinoma (HCC) Insights - HCC is an aggressive cancer with over 900,000 new diagnoses globally each year, and it is projected to become the third leading cause of cancer death by 2030 [4] - The highest incidence and mortality rates of HCC are found in East Asia, with increasing rates in Europe and the US [4] - Chronic liver diseases, including hepatitis B and C, NAFLD, NASH, and cirrhosis, account for 90% of HCC cases [5] Clinical Trial Context - The ongoing global randomized Phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab has shown clinical superiority in overall survival compared to the standard of care [7] - Early-stage HCC patients face a 70-80% recurrence rate post-surgery, which is associated with poorer prognosis [6]