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IF 2.8 Pub Date : 2026-01-01 DOI: 10.1016/S2949-7132(25)00118-1
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引用次数: 0
Right atrial intimal sarcoma with liver metastasis: A case report and literature review 右心房内膜肉瘤伴肝转移1例并文献复习
IF 2.8 Pub Date : 2025-11-06 DOI: 10.1016/j.cpt.2025.11.001
Jiaen You , Zebing Liu , Kang He
Primary cardiac tumors are rare and often present diagnostic challenges due to their non-specific symptoms and imaging characteristics. In this report, we present a case of right atrial intimal sarcoma (IS) with liver metastasis. A 49-year-old woman presented to the emergency department with acute dyspnea, cyanosis, nausea, vomiting, and upper abdominal pain. Echocardiography revealed a large pericardial effusion and a mass in the right atrium. Contrast-enhanced computed tomography (CT) and positron emission tomography/CT (PET/CT) confirmed the presence of multiple nodules in the right atrium and hepatic masses, suggesting metastatic disease. Laboratory tests indicated liver dysfunction, with elevated carbohydrate antigen 125 (CA125) and normal alpha-fetoprotein (AFP) levels. These clinical features initially suggested a diagnosis of hepatocellular carcinoma with isolated cardiac metastasis. However, the final pathological examination and gene sequencing results were unexpected, leading to the diagnosis of right atrial IS with liver metastasis. The patient was managed conservatively and remained alive for 8 months at the time of manuscript submission.
原发性心脏肿瘤非常罕见,由于其非特异性的症状和影像学特征,常常给诊断带来挑战。在此报告中,我们提出一例右心房内膜肉瘤合并肝转移的病例。一名49岁女性因急性呼吸困难、发绀、恶心、呕吐和上腹痛就诊于急诊科。超声心动图显示右心房有大量心包积液和肿块。对比增强CT和正电子发射断层扫描/CT证实右心房存在多发结节和肝脏肿块,提示转移性疾病。实验室检查显示肝功能障碍,碳水化合物抗原125 (CA125)升高,甲胎蛋白(AFP)水平正常。这些临床特征最初提示诊断为肝细胞癌并孤立的心脏转移。但最终病理检查和基因测序结果出乎意料,导致诊断为右心房IS合并肝转移。患者接受保守治疗,在论文提交时存活了8个月。
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引用次数: 0
Targeting immune checkpoint therapy: The role of manganese in tumor immunotherapy 靶向免疫检查点治疗:锰在肿瘤免疫治疗中的作用
IF 2.8 Pub Date : 2025-10-24 DOI: 10.1016/j.cpt.2025.10.001
Xingyao Lyu , Bixia Li , Zhijie Lin
Cancer immunotherapy has emerged as a promising complement to traditional treatments such as radiotherapy and chemotherapy. Although conventional therapies remain central to cancer management, the potential of immunotherapy is increasingly recognized. Immune checkpoint therapy, a key strategy in tumor immunotherapy, has demonstrated significant efficacy against solid tumors. However, its clinical application is hindered by its limited response rate, necessitating efforts to optimize its effectiveness. Recent studies have highlighted the pivotal role of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon gene (STING) pathway in immune checkpoint therapy. Manganese (Mn), an essential trace element, regulates the activity of CD8+ T and NK cells by modulating the cGAS-STING pathway. Furthermore, the combination of Mn with anti-programmed cell death protein 1 therapy has demonstrated promising anti-tumor effects. Mn also influences immunogenic cell death (ICD), further augmenting its potential as an adjunct to tumor immunotherapy. Despite a growing body of research on the role of Mn in modulating the cGAS-STING pathway and inducing ICD, comprehensive reviews that synthesize these findings and explore the potential of Mn in enhancing immune checkpoint therapy are still lacking. This review aimed to fill this gap by examining the immune mechanisms by which Mn enhances immune checkpoint therapy and its overall impact on tumor immunotherapy.
癌症免疫治疗已成为传统治疗如放疗和化疗的一种有希望的补充。虽然传统疗法仍然是癌症治疗的核心,但免疫疗法的潜力越来越被认识到。免疫检查点疗法是肿瘤免疫治疗的一项重要策略,对实体瘤具有显著的疗效。但其有效率有限,阻碍了其临床应用,需要努力优化其疗效。近年来的研究强调了环GMP-AMP合成酶(cGAS) -干扰素基因刺激因子(STING)通路在免疫检查点治疗中的关键作用。锰(Mn)是一种必需的微量元素,通过调节cGAS-STING通路调节CD8+ T和NK细胞的活性。此外,Mn联合抗程序性细胞死亡蛋白1治疗已显示出良好的抗肿瘤效果。锰还影响免疫原性细胞死亡(ICD),进一步增强了其作为肿瘤免疫治疗辅助药物的潜力。尽管越来越多的研究表明Mn在调节cGAS-STING通路和诱导ICD中的作用,但综合这些发现并探索Mn在增强免疫检查点治疗中的潜力的综合综述仍然缺乏。本综述旨在通过研究Mn增强免疫检查点治疗的免疫机制及其对肿瘤免疫治疗的总体影响来填补这一空白。
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引用次数: 0
Cover 封面
IF 2.8 Pub Date : 2025-10-22 DOI: 10.1016/S2949-7132(25)00105-3
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引用次数: 0
Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors: A phase Ib study 顺铂联合辛替单和尼拉帕尼治疗晚期实体瘤的安全性和有效性:一项Ib期研究
IF 2.8 Pub Date : 2025-08-29 DOI: 10.1016/j.cpt.2025.08.005
Haitao Tao , Yining Liu , Lijie Wang , Jinliang Wang , Junxun Ma , Guoqing Zhang , Zhefeng Liu , Yi Hu

Background

Immune checkpoint inhibitors combined with PARP inhibitors and chemotherapy can enhance anti-tumor activity. This phase Ib clinical study was designed to evaluate the safety and efficacy of cisplatin in combination with sintilimab and niraparib in patients with advanced solid tumors.

Methods

Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1–21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers.

Results

From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m2, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% CI: 38.8–NA), objective response rate was 26.92% (7 patients, 95% confidence interval [CI], 11.57–47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92–76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14–4.46) and the median overall survival (OS) was 8.03 months (95% CI: 3.41–12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, P = 0.032) and OS (14.97 months, P = 0.036) compared to those with PD-L1 expression < 1%.

Conclusion

The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.

Trial registration

https://www.chictr.org.cn/; ID: ChiCTR1900024488.
免疫检查点抑制剂联合PARP抑制剂和化疗可增强抗肿瘤活性。该Ib期临床研究旨在评估顺铂联合辛替单抗和尼拉帕尼治疗晚期实体瘤患者的安全性和有效性。方法晚期实体肿瘤患者在接受一种或多种标准治疗后进展,并在第1天接受顺铂和辛替单抗治疗,在第1 - 21天接受尼拉帕尼治疗,每3周持续4个周期,随后使用辛替单和尼拉帕尼维持治疗(与以前相同的剂量和方案),直到疾病进展、死亡或无法忍受的毒性。在剂量递增阶段,根据3 + 3剂量递增方案将患者分为3个剂量组,根据确定的最大耐受剂量(MTD)进行剂量递增阶段。主要终点是安全性,包括治疗相关不良事件(TRAEs)、剂量限制性毒性(DLT)和推荐的2期剂量(RP2D),次要终点是疗效。此外,预先指定了探索性终点来分析潜在的生物标志物。结果2019年7月31日至2022年7月1日,共入组26例患者,在剂量递增阶段未观察到dlt。顺铂、辛替单抗和尼拉帕尼的推荐RP2Ds分别为60mg /m2、200mg和100mg / 3周。所有患者都经历了不同程度的trae,免疫相关不良事件(irAEs)发生率为19.23%(5例)。中位随访时间为47.9个月(95% CI: 38.8-NA),客观缓解率为26.92%(7例,95%可信区间[CI], 11.57-47.79),疾病控制率为57.69%(15例,95% CI: 36.92-76.65),中位无进展生存期(PFS)为3.30个月(95% CI: 2.14-4.46),中位总生存期(OS)为8.03个月(95% CI:3.41-12.66), 6、12个月时PFS分别为26.92%(7例)和11.54%(3例),6、12、24个月时OS分别为69.23%、34.62%和11.54%。与PD-L1表达≥1%的患者相比,程序性细胞死亡配体1 (PD-L1)表达≥1%的患者PFS(3.93个月,P = 0.032)和OS(14.97个月,P = 0.036)明显延长。结论顺铂联合西替单抗和尼拉帕尼治疗晚期实体瘤具有可控的安全性和适度的抗肿瘤活性。需要在更大的组织学特异性患者中进一步验证以确认临床益处。审判registrationhttps: / / www.chictr.org.cn/;ID: ChiCTR1900024488。
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引用次数: 0
Cover 封面
IF 2.8 Pub Date : 2025-08-29 DOI: 10.1016/S2949-7132(25)00084-9
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引用次数: 0
Exploring marine-derived compounds as potential anti-cancer agents: Mechanisms and therapeutic implications 探索海洋衍生化合物作为潜在的抗癌剂:机制和治疗意义
IF 2.8 Pub Date : 2025-08-26 DOI: 10.1016/j.cpt.2025.08.004
Nagaraju Bandaru , Yash Pramod Patil , Sumit Dilip Ekghara , Kunal Sharad patil , Mohan Gandhi Bonthu
Marine-derived compounds have emerged as a promising frontier in cancer research due to their remarkable structural diversity and broad-spectrum bioactivities. The marine environment, encompassing diverse organisms (e.g., sponges, algae, tunicates, mollusks, and marine microbes), is a prolific source of novel bioactive molecules with potent anti-cancer properties. Key classes of these compounds include alkaloids, polysaccharides, peptides, terpenoids, and polyketides, which exert anti-tumor effects through diverse mechanisms, including the induction of apoptosis, inhibition of angiogenesis, modulation of immune responses, interference with cell cycle progression, and targeting of critical signaling pathways involved in tumorigenesis and metastasis. Notably, marine-derived drugs such as trabectedin, eribulin, and plitidepsin have received regulatory approval for the treatment of various malignancies, demonstrating the translational potential of these natural compounds. Ongoing clinical and preclinical investigations are exploring a wide range of marine metabolites for their cytotoxic, anti-proliferative, and chemosensitizing properties. Advances in marine biotechnology, including genome mining, synthetic biology, and fermentation technologies, have significantly facilitated the discovery, sustainable production, and structural optimization of marine natural products. However, challenges such as low yield, structural complexity, limited water solubility, and poor bioavailability hinder their broader clinical application. The integration of novel drug delivery systems, such as nanoparticles, liposomes, and conjugates, offers a viable solution to overcome these limitations and improve pharmacokinetic profiles. This review provides a comprehensive overview of the mechanisms of action, therapeutic applications, and clinical development of marine-derived anti-cancer compounds. It also emphasizes the need for deeper insights into their molecular targets and the potential for synergistic use with existing chemotherapeutic agents. Future directions should focus on exploring untapped marine biodiversity, developing eco-friendly harvesting strategies, and developing innovative delivery platforms to fully harness the therapeutic promise of the marine pharmacopeia in oncology.
海洋来源的化合物由于其显著的结构多样性和广谱生物活性而成为癌症研究的一个有前途的前沿。海洋环境包括多种生物(如海绵、藻类、被囊动物、软体动物和海洋微生物),是具有有效抗癌特性的新型生物活性分子的丰富来源。这些化合物的关键类别包括生物碱、多糖、多肽、萜类和多酮类,它们通过多种机制发挥抗肿瘤作用,包括诱导细胞凋亡、抑制血管生成、调节免疫反应、干扰细胞周期进程,以及靶向肿瘤发生和转移的关键信号通路。值得注意的是,海洋衍生药物如trabectedin、eribulin和plitidepsin已获得监管机构批准,可用于治疗各种恶性肿瘤,证明了这些天然化合物的转化潜力。正在进行的临床和临床前研究正在探索广泛的海洋代谢物的细胞毒性、抗增殖和化学致敏特性。海洋生物技术的进步,包括基因组挖掘、合成生物学和发酵技术,极大地促进了海洋天然产物的发现、可持续生产和结构优化。然而,产率低、结构复杂、水溶性有限和生物利用度差等挑战阻碍了它们更广泛的临床应用。新型药物传递系统的整合,如纳米颗粒、脂质体和缀合物,为克服这些限制和改善药代动力学特征提供了可行的解决方案。本文综述了海洋来源的抗癌化合物的作用机制、治疗应用和临床研究进展。它还强调需要更深入地了解它们的分子靶点以及与现有化疗药物协同使用的潜力。未来的方向应该集中在探索尚未开发的海洋生物多样性,开发生态友好的收获策略,开发创新的输送平台,以充分利用海洋药典在肿瘤学中的治疗前景。
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引用次数: 0
Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance 研究癌症中的缺氧诱导因子信号:机制、临床意义、靶向治疗策略和耐药性
IF 2.8 Pub Date : 2025-07-12 DOI: 10.1016/j.cpt.2025.07.003
Abdul Halim Shaikat , S.M. Asadul Karim Azad , Md Azizur Rahman Tamim , Mohammed Sailim Ullah , Mohammad Nurul Amin , Mofazzal K. Sabbir , Md Towhidul Islam Tarun , Md Saqline Mostaq , Shohana Sabrin , Md Zihad Mahmud , Md Ashiq Mahmud
Hypoxia, a hallmark of the tumor microenvironment (TME), drives cancer progression through immune modulation, angiogenesis promotion, metabolic reprogramming, and uncontrolled cell proliferation. This review explores the diverse functions of hypoxia-inducible factor (HIF) signaling in cancer development and progression, providing a comprehensive overview of the molecular pathways. HIFs, particularly HIF-1α and HIF-2α, regulate several genes related to cancer hallmarks such as invasion, metabolic reprogramming, angiogenesis, and therapy resistance, thus mediating a significant portion of the hypoxic response. Hydroxylation of proline and asparagine residues in HIF-α subunits, which occurs in an oxygen-dependent manner, serves as a key regulatory mechanism for both their stability and transcriptional function. Notably, this complex interaction is regulated by multiple signaling pathways, including the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. In cancer, HIF signaling affects several aspects of tumor cell biology that contribute to the cancerous characteristics, including angiogenesis induction through the upregulation of vascular endothelial growth factor (VEGF) expression, metabolic reprogramming through the enhancement of the Warburg effect, facilitation of cancer invasion and metastasis by driving epithelial-to-mesenchymal transition (EMT) and matrix remodeling patterns, and mediation of therapeutic resistance partly due to the effects on drug efflux pumps and DNA damage repair. Direct and indirect HIF inhibitors—including small molecules, peptidomimetics, antibodies, and proteolysis-targeting chimeras (PROTACs)—are under preclinical and clinical evaluation for their therapeutic efficacy. Preclinical and early clinical trials have demonstrated significant synergistic effects in inhibiting tumor development when HIF inhibition is combined with traditional therapies (chemotherapy or radiation) or immunotherapies, emphasizing major clinical implications and the potential for improving patient outcomes. Although challenges exist, particularly regarding drug resistance, further research to improve therapeutic efficacy and prolong survival for patients is warranted.
缺氧是肿瘤微环境(TME)的标志,通过免疫调节、血管生成促进、代谢重编程和不受控制的细胞增殖驱动癌症进展。本文综述了缺氧诱导因子(HIF)信号在癌症发生和发展中的多种功能,并对其分子通路进行了全面的综述。hif,特别是HIF-1α和HIF-2α,调节与癌症特征相关的几个基因,如侵袭、代谢重编程、血管生成和治疗抵抗,因此介导了缺氧反应的重要部分。HIF-α亚基中脯氨酸和天冬酰胺残基的羟基化以氧依赖的方式发生,是其稳定性和转录功能的关键调控机制。值得注意的是,这种复杂的相互作用受到多种信号通路的调节,包括细胞外信号调节激酶/丝裂原活化蛋白激酶(ERK/MAPK)、磷酸肌苷3-激酶/蛋白激酶B/雷帕霉素机制靶点(PI3K/Akt/mTOR)和Janus激酶/信号转导和转录激活因子(JAK/STAT)通路。在癌症中,HIF信号影响肿瘤细胞生物学的几个方面,这些方面有助于癌症特征,包括通过上调血管内皮生长因子(VEGF)表达诱导血管生成,通过增强Warburg效应促进代谢重编程,通过驱动上皮-间质转化(EMT)和基质重塑模式促进癌症侵袭和转移。以及部分由于药物外排泵和DNA损伤修复的影响而介导的治疗抗性。直接和间接的HIF抑制剂——包括小分子、肽模拟物、抗体和靶向蛋白水解嵌合体(PROTACs)——正在临床前和临床评估其治疗效果。临床前和早期临床试验表明,当HIF抑制与传统疗法(化疗或放疗)或免疫疗法联合使用时,在抑制肿瘤发展方面具有显著的协同作用,强调了主要的临床意义和改善患者预后的潜力。尽管存在挑战,特别是在耐药性方面,但有必要进一步研究以提高治疗效果并延长患者的生存期。
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引用次数: 0
Improving research transparency: An interpretation of the updated consolidated standards of reporting trials 2025 guideline from the perspective of clinical trials in oncology 提高研究透明度:从肿瘤学临床试验的角度解读最新的综合试验报告标准2025指南
IF 2.8 Pub Date : 2025-07-08 DOI: 10.1016/j.cpt.2025.07.002
Yaguang Peng , Peng Lyu , Xiaoxia Peng
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引用次数: 0
Neuroendocrine prostate cancer (NEPC)-associated CEP55 promotes cisplatin resistance in prostate cancer by regulating CDK1 phosphorylation 神经内分泌前列腺癌(NEPC)相关的CEP55通过调节CDK1磷酸化促进前列腺癌的顺铂耐药
IF 2.8 Pub Date : 2025-07-05 DOI: 10.1016/j.cpt.2025.06.008
Zhuocheng Lai , Chenxi Hu , Jirong Jie , Yongyuan Xiao , Yuanchao Zhu , Xueni Guo , Yintong Liu , Yiwei Wang , Shiyu Pang , Xiangbo Zeng , Wanlong Tan , Qiong Wang
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and dataset analyses identified Centrosomal Protein 55 (CEP55) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that CEP55 is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while CEP55 show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, CEP55 has been shown to regulate cisplatin resistance through the phosphorylation of CDK1 at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.
神经内分泌前列腺癌(NEPC)是去势抵抗性前列腺癌(CRPC)的一种侵袭性亚型,对目前几乎所有的治疗方法都具有典型的抗性。在这项研究中,单细胞RNA测序(scRNA-seq)和数据集分析发现,中心体蛋白55 (CEP55)是激素敏感性前列腺癌(HSPC)向CRPC转化并最终向NEPC转化的关键因素。随后的生物信息学分析和临床样本验证表明,与HSPC和CRPC相比,CEP55在NEPC组织中显著上调。此外,虽然CEP55与免疫微环境或癌症相关成纤维细胞(CAFs)没有显著关联,但我们的研究结果表明,它直接介导前列腺癌细胞的可塑性,从而推动NEPC的进展。具体而言,体内和体外实验证实,CEP55可增强前列腺癌细胞的增殖、迁移、侵袭以及NEPC生物标志物的表达。重要的是,虽然顺铂是临床上NEPC的主要治疗方法,但CEP55已被证明通过酪氨酸15 (Tyr15)位点CDK1的磷酸化来调节顺铂耐药性。总之,我们的研究确定了一个影响前列腺癌神经内分泌分化过程的关键基因,表明其可能是一个重要的治疗靶点。
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引用次数: 0
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Cancer pathogenesis and therapy
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