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].