撰文丨王聪 编辑丨王多鱼 排版丨水成文 以 PD-1/PD-L1 抑制剂为代表的 免疫检查点阻断 （ICB） 疗法，这地改变了癌症治疗格局，但其带来的 治疗益处可能会因免疫相关不良事件 （irAE） 的发生而被削弱。 因此，识别出介导 免疫相关不良事件 （irAE） 而又 不影响治疗疗效的的毒性特异性分子，有望从根源上 阻止 irAE 的发生发展，从而实现在不降低抗肿瘤疗效的情况下，减轻毒性。 2026 年 3 月 5 日，南方医科大学南方医院 董忠谊 、 吴德华 、 刘莉 作为共同通讯作者 （ 马思聪 、 容 子轩 等人论文共同第一作者 ） ，在 Nature 子刊 Nature Cancer 上发表了题为： CRTAM inhibition mitigates toxicity of immune checkpoint inhibitors without antitumor efficacy trade-off 的研究论文。 该研究发现了 在不降低 免疫检查点阻断 （ICB） 疗法的 抗肿瘤效果的情况下减轻毒性的新靶点 —— CRTAM ， 抑制 CRTAM，可减轻免疫检查点抑制剂的毒性，而不影响其抗肿 ...

这提示了我们，癌症免疫治疗中可能存在着一种 内在随机性 ，这意味着，即使我们将来对所有已知的确定性机制都了如指掌，这种内在随机性为癌症免疫疗法的 成功设定了一个理论上限，导致我们无法完全预测治疗结局。 2026 年 2 月 5 日，美国国家癌症研究中心的研究人员在国际顶尖学术期刊 Cell 上发表了题为： Stochasticity in cancer immunotherapy stems from rare but 撰文丨王聪 编辑丨王多鱼 排版丨水成文 functionally critical Spark T cells 的研究论文。 癌症免疫疗法这一不断扩大的领域，很大程度上得益于过继 T 细胞疗法和/或检查点抑制疗法在一小部分传统疗法 （放疗、化疗和手术） 无效癌症患者身上取得 的成功。然而，大多数癌症患者对癌症免疫疗法仍无良好响应，这可能是由于肿瘤细胞的遗传或表观遗传改变、环境因素、缺乏适当的肿瘤特异性 T 细胞以及肿 瘤浸润淋巴细胞 （TIL） 的耗竭表型所致。所有这些因素都是决定性的，这意味着对这些机制有更深入的理解应该足以准确预测每位患者对癌症免疫疗法的响应 或抵抗情况。 该研究表明，癌症 ...

Core Insights - The article highlights the ongoing battle against cancer, emphasizing the need for improved patient survival and treatment development, particularly in China, where cancer incidence and mortality rates are the highest globally [1][2] Group 1: Cancer Statistics and Survival Rates - In 2022, approximately 970 million people died from cancer globally, with China reporting the highest new cases and deaths [1] - From 2019 to 2021, China's age-standardized five-year relative survival rate for cancer improved to 43.7% [1] - Lung cancer remains a significant concern, with 2022 data showing 1.0606 million new cases in China, accounting for 22% of all malignant tumors [5] Group 2: Advances in Cancer Treatment - Innovative therapies such as immunotherapy and targeted therapy are providing more treatment options for cancer patients, contributing to improved survival rates [1][4] - The five-year survival rate for lung cancer has reached approximately 32%, an increase of 8% compared to previous chemotherapy-only treatments [5][6] - New treatment regimens, particularly targeted therapies, have shown significant survival benefits, with some patients experiencing overall survival of up to 47 months [5][6] Group 3: Challenges in Cancer Management - Despite advancements, challenges remain, including the need for improved early screening and diagnosis, particularly in lung cancer [7] - Drug resistance in immunotherapy poses a significant barrier to treatment effectiveness, with many clinical trials facing challenges [7] - There is a gap in patient education regarding new treatment options, which hinders informed decision-making [7] Group 4: Future Outlook and Collaboration - The industry anticipates over 100 new cancer drugs to be launched globally in the next five years, which will require enhanced drug accessibility and management of adverse reactions [9] - The vision of transforming cancer into a manageable chronic disease necessitates collaboration among healthcare providers, pharmaceutical companies, and patient organizations [9]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 2026 年 1 月 29 日，著名癌症学家 Douglas Hanahan 在国际顶尖学术期刊 Cell 上发表了关于" 癌症特征 "理论的最新综述 —— Hallmarks of cancer—Then and now, and beyond 。这距离他与 Robert Weinberg 首次提出癌症特征理论已过去了 26 年，当时他们提出的 癌症的六大特征 彻底改变了人们对癌症的理 解。 如今， 这一理论框架已经扩展为 九大特征 ，并加入了 四个理解维度 ，为癌症研究和治疗提供了更为全面的路线图。 癌症特征的演变：从六个到九个 2000 年， Douglas Hanahan 和 Robert Weinberg 在 Cell 期刊发表综述论文， 首次提出了 癌症的六大特征 —— 维持增殖信号 、 失活生长抑制因子 、 抵抗 程序性细胞死亡 、 建立复制永生性 、 诱导或获取血管生成 、 激活侵袭和转移 。 2011 年，他们增加了两大新特征： 解除细胞代谢调控 、 逃逸免疫摧毁 。2022 年， Douglas Hanahan 加入了第九个特征—— 解锁表型可塑性 ...

Core Insights - Chinese companies are projected to conduct approximately 39% of global cancer clinical trials in 2024, surpassing the United States at about 32% [2][8] - The number of clinical trials in China has increased significantly, from around 2% in 2009 to approximately 35% in 2023, indicating a growing dominance in the cancer research field [2][8] - The Chinese government is providing strong support for new drug research, designating it as a key national focus and investing substantial resources [4][8] Clinical Trials and Market Dynamics - In 2024, Chinese enterprises are expected to conduct 896 cancer clinical trials, leading globally, while the U.S. will conduct 720 trials [2][8] - The total number of clinical trials globally is projected to be 5,318, with Chinese companies accounting for 1,669 trials, approximately 30% of the total [7][8] - The increase in patient numbers in China facilitates easier clinical trial execution and drug development [5] Collaborations and Partnerships - Japanese pharmaceutical companies are increasingly collaborating with Chinese firms, with notable agreements in cancer treatment and autoimmune disease therapies [6][7] - In 2023, Takeda Pharmaceutical signed an agreement with a Chinese company for cancer drug licensing, highlighting the advantages of conducting research in China [6][7] - By mid-2025, contracts between Chinese and global pharmaceutical companies are expected to exceed $48.5 billion, indicating a robust partnership trend [7] Intellectual Property and Globalization - China filed over 188,000 drug patents in 2024, significantly outpacing the U.S. with about 53,000 patents, reflecting a rapid enhancement in research capabilities [7][8] - For Chinese drugs to enter international markets, they must undergo rigorous clinical trials and secure regulatory approvals, emphasizing the importance of intellectual property protection [10] - The potential for innovative Chinese drugs to be utilized globally is increasing, necessitating careful management of economic and geopolitical risks [10]

Core Viewpoint - Chinese companies are leading the world in cancer clinical trials, with a projected 39% share in 2024, surpassing the United States at 32% and indicating a significant shift in the global pharmaceutical landscape [1][3]. Group 1: Clinical Trials and Market Position - In 2024, Chinese enterprises are expected to conduct 896 cancer clinical trials, representing 39% of the global total, while the U.S. will account for approximately 32% [3]. - The number of clinical trials conducted by Chinese companies has increased from about 2% in 2009 to 35% in 2023, marking a substantial growth trajectory [3]. - The global market for pharmaceuticals is projected to see China’s drug expenditure reach $166 billion in 2024, constituting 10% of the global market [9]. Group 2: Government Support and R&D Investment - The Chinese government has prioritized new drug research as a key area, providing substantial funding and talent, particularly in the biopharmaceutical sector [7]. - The "Made in China 2025" initiative has identified biomedicine as a critical industry for national revitalization [7]. Group 3: Collaborations and Partnerships - Japanese pharmaceutical companies are increasingly collaborating with Chinese firms, with notable agreements for cancer treatments and other therapeutic areas [8]. - In the first half of 2025, contracts between Chinese and global pharmaceutical companies reached 61, totaling $48.5 billion, indicating a growing trend in international partnerships [9]. Group 4: Innovation and Patent Applications - China applied for over 188,000 drug patents in 2024, significantly outpacing the U.S. with approximately 53,000 applications, showcasing an increase in R&D capabilities [9]. - The quality of drug development in China is improving, with expectations for the emergence of blockbuster drugs and major pharmaceutical companies in the future [9]. Group 5: Global Market Challenges - Despite advancements, Chinese drugs primarily remain within the domestic market, with challenges in gaining approval for international sales [11]. - The need for transparent clinical trial data and intellectual property protection is crucial for Chinese companies aiming for global market entry [12].

Core Viewpoint - The study highlights that high-dose ascorbic acid can selectively induce pyroptosis in LKB1-deficient non-small cell lung cancer (NSCLC) cells and enhance their sensitivity to immune checkpoint inhibitors (ICIs) [4][6]. Group 1: LKB1 Deficiency and Immune Resistance - LKB1 mutations lead to primary resistance to ICIs in NSCLC, characterized by a "cold tumor" subtype with insufficient Tpex cell infiltration [2][6]. - Tpex cells, which are crucial for responding to PD-1/PD-L1 blockade therapies, show high expression levels of the transcription factor TCF1 [2]. Group 2: Mechanism of Action - High-dose ascorbic acid exacerbates oxidative stress in LKB1-deficient NSCLC cells by upregulating the transporter GLUT1, leading to increased accumulation of ascorbic acid [6][8]. - The oxidative stress triggers pyroptosis in LKB1-deficient NSCLC cells through the H₂O₂/ROS-caspase-3-GSDME signaling axis [6][8]. Group 3: Clinical Implications - In preclinical models, high-dose ascorbic acid reverses ICI resistance and reshapes the immune microenvironment characterized by TCF1+ CD8+ T cell infiltration [7][8]. - Pyroptosis-driven immunogenic cell death promotes the maturation of cross-presenting dendritic cells, which is essential for Tpex cell expansion [7][8]. - The study provides a theoretical basis for clinical trials combining ICIs with high-dose ascorbic acid [7][8].