Paclitaxel

近日，南华大学附属第一医院研究团队在期刊《Journal of Experimental&Clinical Cancer Research》上发表了题为“Ferrodoxin 1 (FDX1) drives paclitaxel resistance in ovarian cancer via copper metabolism and ULK1/ATG13-mediated autophagy: overcome by pH/ROS-responsive PPD/PDP@si-FDX1 nanomicelles”的研究论文，本研究发现FDX1 过表达会提高细胞内铜含量，激活 ULK1/ATG13 自噬轴，并增强紫杉醇耐药性；沉默 FDX1 则可逆转这些效应。铜螯合剂或 ULK1 抑制可模拟 FDX1 沉默的效果。PPD/PDP@si-FDX1 表现出 pH/ROS 响应性肿瘤蓄积，并增强了 si-FDX1 的递送。在体内实验中，它显著抑制肿瘤生长并恢复紫杉醇敏感性，优于游离的 si-FDX1。FDX1 通过铜依赖的 ULK1/ATG13 激活驱动 TAX 耐药性；PPD/PDP@si-FDX1 纳米胶束有效逆转耐药性，为卵巢癌治疗提供了一种有前景的策略。 卵巢癌：现状、治疗困境与紫杉醇耐药性挑战 01 卵巢癌（OC）是女性生殖系统中最常见的恶性肿瘤之一，全球每年有成千上万的新发病例。它约占所有女性癌症的 3.7%，占癌症相关死亡的 4.7%。尽管近年来早期筛查和诊断技术有所进步，但由于早期症状不明显，卵巢癌往往在晚期才被发现，导致大多数患者预后不良。卵巢癌的主要治疗方法是手术切除和化疗，紫杉醇（TAX）是首选的化疗药物。紫杉醇通过稳定微管蛋白聚合发挥抗肿瘤作用，抑制肿瘤细胞的分裂和增殖。然而，对紫杉醇的耐药性是临床上的一个重大挑战，导致治疗效果不佳和预后恶化。紫杉醇耐药性已成为卵巢癌治疗的一个重要障碍，这凸显了阐明其机制和开发新方法以提高治疗效果的重要性。 PPD/PDP@si-FDX1 在体内表现出增强的抗肿瘤功效 02 研究人员通过不同治疗组肿瘤组织的 H&E 和 TUNEL 染色进一步评估了 PPD/PDP@si-FDX1 纳米胶束的体内抗肿瘤性能。生理盐水组和 PPD/PDP 组之间未检测到明显的组织病理学差异，证实了载体的生物安全性。相比之下，si-FDX1 和 PPD/PDP@si-FDX1 治疗均诱导了不同程度的肿瘤坏死和细胞凋亡，其中 PPD/PDP@si-FDX1 组的效果最为显著。这些结果表明，PPD/PDP 胶束显著提高了药物的递送效率和生物利用度。沉默 FDX1 进一步增强了 TAX 的抗肿瘤效果并降低了其耐药性。总体而言，PPD/PDP@si-FDX1 纳米系统在体内表现出卓越的抗肿瘤功效。 通过免疫荧光和 WB 分析，以及对肿瘤组织中自噬相关蛋白表达和铜离子水平的测定，进一步验证了 PPD/PDP@si-FDX1 在体内的沉默效果。与生理盐水组相比，si-FDX1 和 PPD/PDP@si-FDX1 治疗组均表现出 FDX1、P-ULK1、P-ATG13 和 LC3B-II/I 的显著下调，同时 P62 显著上调。si-FDX1 和 PPD/PDP@si-FDX1 组的铜死亡水平均显著降低。这些发现与体外结果一致，并证实了 PPD/PDP@si-FDX1 的抗肿瘤活性与通过 ULK1–ATG13 信号轴介导的铜调节和自噬抑制密切相关。与 si-FDX1 组相比，PPD/PDP@si-FDX1 治疗组 FDX1、P-ULK1、P-ATG13 和 LC3B-II/I 的下调更为显著，同时 P62 表达显著增加。此外，该组的铜死亡水平进一步下降。这些结果共同表明，PPD/PDP 纳米系统提高了 si-FDX1 的生物利用度和沉默效率，从而更有效地抑制了自噬和铜诱导的信号传导。 PPD/PDP@si-FDX1 的体内抗肿瘤活性 研究意义 03 这些研究结果凸显了 FDX1 作为潜在治疗靶点的重要性，并证明了基于纳米技术的 siRNA 递送系统在克服卵巢癌耐药性方面的前景。 参考资料： https://link.springer.com/article/10.1186/s13046-025-03589-z 【关于投稿】 转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！ 转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。 责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！ 微信号：zhuanhuayixue

Taylor Tieden for BioSpace The FDA is looking at a slew of label expansions this month, including one that could open up home-based treatments for Alzheimer’s disease. With just a handful of target action dates lined up, May is shaping up to be a relatively quiet month for the FDA. Still, the regulator’s verdicts this month could have far-reaching implications for biopharma, including broadening patient pools for a couple of drugmakers and opening up at-home treatment for one of only two disease-modifying therapies on the market for Alzheimer’s disease. Read below for more. Argenx eyes ‘broadest label’ for myasthenia gravis drug Argenx is looking to expand the label of its generalized myasthenia gravis (gMG) drug Vyvgart to cover patients who are seronegative for acetylcholine receptor (AChR) antibodies, a key disease marker. Approved in December 2021 for gMG, Vyvgart is currently only indicated for patients positive for AChR antibodies. The FDA is reviewing this proposal, with a decision expected by May 10. If approved, Vyvgart would boast “the broadest label” of all drugs in its class approved for gMG, analysts at William Blair wrote in an Aug. 25, 2025 note. Argenx would add approximately 11,000 more patients to its total addressable population, according to the firm. Vyvgart is an IgG1 antibody fragment that works by blocking the neonatal Fc receptor (FcRn), in turn lowering the overall circulating levels of IgG, a type of immune system antibody that attacks AChR receptors and drives gMG pathology . Common gMG symptoms include muscle weakness that affects the limbs, leading to fatigue, difficulty walking and problems speaking or eating. To support the proposal for a broader label, Argenx filed data from the Phase 3 ADAPT SERON study, which enrolled patients with three gMG subtypes, all of which were negative for AChR. Patients in the trial had gMG that was either MuSK-positive, LRP4-positive or negative for all three markers. Data showed “clinically meaningful” improvements in disease severity and activities of daily life after Vyvgart treatment, according to a January press announcement . Vyvgart was also well-tolerated, with no new safety concerns arising. AstraZeneca, Daiichi Sankyo make neoadjuvant push for breast cancer drug After notching a label expansion in January 2025, AstraZeneca and Daiichi Sankyo are keeping up the pace for their breast cancer antibody-drug conjugate (ADC) Enhertu. The pharma partners are now proposing to use the drug in a neoadjuvant setting—ahead of surgery—for patients with HER2-positive stage 2 or stage 3 breast cancer. The FDA’s target action date for this application is May 18. The companies are backing their bid with data from the Phase 3 DESTINY-Breast11 study. A readout in October 2025 showed that Enhertu—followed by a course of paclitaxel, trastuzumab and pertuzumab (THP)—resulted in a 67.3% pathologic complete response rate in patients with high-risk, locally-advanced disease who hadn’t yet undergone resection. This effect was the “highest reported pathologic complete response rate seen in a Phase 3 registrational trial for HER2-positive early breast cancer,” AstraZeneca and Daiichi Sankyo claimed at the time. Controls in DESTINY-Breast11 received a dose-dense cycle of doxorubicin and cyclophosphamide plus THP, yielding a pathologic complete response rate of 56.3%. The overall treatment effect was 11.2% in favor of the Enhertu regimen. Enhertu has been on somewhat of a winning streak of late. In January 2025, the FDA signed off on the drug’s use in breast cancer patients with ultralow expression levels of HER2. Then, in December last year, the ADC again cleared the FDA’s regulatory bar for frontline use in patients with HER2-positive breast cancer—an approval that Jefferies analysts in a Dec. 16 note estimated would add $2 billion to $3 billion to peak sales. Eisai, Biogen seek induction nod for SubQ Leqembi In September 2025, Eisai and Biogen won the FDA’s go-ahead for an under-the-skin injection of their anti-amyloid Alzheimer’s therapy Leqembi—though the approval applied only to the maintenance use of the drug for patients who have already been on Leqembi for 18 months. Now, the partners are proposing a similar subcutaneous injection formulation to initiate patients on the treatment. The FDA’s decision is expected on or before May 24. Supporting the companies’ application are data from sub-studies of the Phase 3 Clarity AD trial, demonstrating that under-the-skin injections of Leqembi across various doses resulted in comparable drug exposure to an intravenous course given every two weeks. Biomarker and safety outcomes were likewise similar between the two regimens. If approved, the subcutaneous formulation would allow for the at-home initiation of patients onto Leqembi therapy and open up a subcutaneous regimen for the entirety of their treatment journey, Biogen and Eisai said in a Jan. 25 release . Cingulate’s ADHD drug nears FDA verdict On or before May 31, the FDA is expected to release its decision regarding Cingulate Inc’s daily tablet CTx-1301 for attention deficit/hyperactivity disorder (ADHD). CTx-1301 is a reformulated version of dexmethylphenidate, a stimulant of the central nervous system that has been validated for the treatment of ADHD and is the active ingredient in Novartis’ Focalin. Cingulate’s version, which makes use of the company’s proprietary Precision Timed Release technology, is designed to deliver three doses at specific points during the day, according to the company’s website . This release pro meant to “deliver the right amount of drug at the right time when patients need it,” ensuring rapid therapeutic activity and whole-day efficacy. The FDA is reviewing CTx-1301 under the agency’s 505(b)(2) pathway, which allows sponsors to reference existing data on previously approved active ingredients, buffing it up with evidence of added benefit through a differentiated delivery mechanism, according to Cingulate. To satisfy this requirement, the biotech filed Phase 3 findings showing that CTx-1301 led to symptom relief assessed through different metrics, both in pediatric and adult populations. Cingulate also showed that CTx-1301’s novel formulation was safe, with no serious treatment-emergent adverse events.