来源：科技日报 科技日报北京12月28日电 （记者张佳欣）据最新一期《自然·通讯》杂志报道，德国德累斯顿工业大学 牵头的国际研究团队发现，在癌症的两大经典特征——逃避细胞凋亡和能量代谢失调背后，存在共同的 分子调控机制。长期被视为"抗凋亡因子"的蛋白质MCL1，不仅帮助癌细胞"活下来"，还直接参与调控 其能量与生长信号。 研究团队认为，这项研究代表科学家对癌症分子基础理解的重大进展。尤其是，破解MCL1抑制剂心脏 毒性难题，对推动相关疗法重新进入临床具有关键意义。 研究表明，MCL1还能直接影响mTOR信号通路。mTOR是细胞整合营养、能量和生长信号的核心因 子，决定细胞在何种条件下生长和增殖。实验显示，MCL1与mTORC1复合体存在直接功能联系，从而 影响癌细胞的能量供给和代谢状态。 这一发现意味着，MCL1在肿瘤中的作用不仅限于阻止细胞凋亡，还深度参与能量与生长信号调控，将 两种原本相对独立的癌症机制联系在一起。 此外，研究还解决了长期困扰临床的问题。以往多项MCL1抑制剂临床试验因严重心脏毒性被迫中止， 此次研究首次阐明了这种毒性的分子机制，并提出饮食干预策略，可显著降低心脏损伤风险。 细胞凋亡是机体 ...

Core Viewpoint - Ascenta Therapeutics, now known as Ascent Pharma, has transformed from a near-bankrupt startup to a globally recognized player in the biopharmaceutical industry, achieving significant milestones such as dual listings in Hong Kong and NASDAQ, and securing a $1.3 billion partnership with Takeda Pharmaceutical [2][5][26]. Group 1: Company Evolution - The company was founded in 2003 by three scientists in Pennsylvania, focusing on innovative cancer therapies targeting apoptosis pathways [9]. - After facing severe setbacks, including the failure of the Bcl-2 inhibitor AT-101 and the 2008 financial crisis, the company was on the brink of collapse but chose to continue operations in China [10][12]. - From 2009 to 2014, the company focused on survival and redefined its research direction towards safer apoptosis-targeting drugs, laying the groundwork for future successes [13]. Group 2: Product Development and Financial Growth - The third-generation BCR-ABL inhibitor, Nairike, was approved in China and became a significant revenue driver, contributing 2.17 billion yuan in sales by mid-2025, representing over 90% of the company's revenue [6][23]. - The company secured a $1.3 billion global collaboration with Takeda in 2024, marking a record for Chinese small molecule drugs in international partnerships [5][26]. - Ascent Pharma's product pipeline has expanded to include multiple promising candidates, establishing a comprehensive portfolio in apoptosis-targeting therapies [34]. Group 3: Market Position and Future Prospects - The dual listing on NASDAQ in January 2025 marked a significant milestone, allowing the company to access global capital markets and enhance its valuation [36]. - The company is now positioned to leverage its successful products and partnerships to drive further growth and innovation in the global biopharmaceutical landscape [41]. - Future focus areas include the market penetration of Nairike, the competitive positioning of its products like APG-2575, and the potential of its pipeline to replicate the success of its leading products [43][44].

Core Insights - A key gene mutation in the human immune protein Fas ligand (FasL) may increase cancer susceptibility in humans compared to close relatives like chimpanzees, providing important clues for developing new cancer therapies [1][2] Group 1: Research Findings - The study published in Nature Communications highlights that elevated levels of plasmin, a protease, in the tumor microenvironment act like "molecular scissors" that cut mutated FasL, leading to a loss of its anti-cancer function [1] - This unique vulnerability in humans explains why immunotherapies like CAR-T are effective against blood cancers but struggle with solid tumors such as triple-negative breast cancer, as blood cancer cells do not rely on plasmin for dissemination [1] Group 2: Implications for Treatment - The mutation in FasL may have contributed to increased brain capacity in humans but also poses a risk for higher cancer susceptibility, suggesting a potential "key" to unlocking immunotherapy [2] - Blocking plasmin or protecting FasL could reactivate the immune system's anti-cancer capabilities, offering new strategies for treating challenging cancers like triple-negative breast cancer through the combined use of plasmin inhibitors and existing therapies [2]

Core Viewpoint - The research conducted by the team led by Academician Shi Yigong reveals the structural basis of BAX pore formation, which is crucial for understanding mitochondrial outer membrane permeability during apoptosis [2][3]. Group 1: Research Findings - The study elucidates the assembly principles of various BAX oligomers, providing a structural foundation for BAX-mediated mitochondrial outer membrane permeability [3]. - The research team purified recombinant human BAX protein and confirmed its membrane permeability activity through cytochrome c release experiments based on liposomes [5]. - The activated BAX oligomers were extracted and purified from overexpressed BAX protein in human embryonic kidney 293F cells for cryo-electron microscopy analysis [6]. Group 2: Structural Insights - The study identified that the dimer of BAX is the basic repeating structural unit of its various oligomeric forms (arc, line, and ring) [7]. - The structure of the BAX repeating unit revealed interactions within and between dimers, with the α9 helix facilitating end-to-end stacking to form linear, arc, polygonal, and ring shapes [7]. - Structural characterization was performed on quadrilateral, pentagonal, hexagonal, and heptagonal forms composed of 16, 20, 24, and 28 BAX monomers, respectively [7]. Group 3: Implications of Findings - The results clarify how activated BAX oligomers permeabilize (or rupture) the mitochondrial outer membrane and explain how different shapes (arc, line, and ring) are assembled from the same repeating unit [9].

Core Insights - Scientists from Walter and Eliza Hall Institute in Australia have discovered a small molecule that can selectively inhibit apoptosis, which opens new avenues for treating neurodegenerative diseases such as Parkinson's and Alzheimer's [1] Group 1 - The research findings were published in the latest issue of the journal "Science Advances" [1]