预约演示

更新于：2026-07-01

Cisplatin

顺铂

更新于：2026-07-01

概要

基本信息

药物类型

小分子化药

别名

CACP、CDDP、CIS-DDP

+ [27]

靶点

DNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)

治疗领域

肿瘤免疫系统疾病消化系统疾病+ [9]

在研适应症

胆道癌头颈部鳞状细胞癌恶性胸膜间皮瘤+ [72]

非在研适应症

食管腺癌晚期胆管癌晚期宫颈癌+ [97]

原研机构

HQ Specialty Pharma Corp.

Privo Technologies, Inc.

在研机构

Amgen, Inc.

Bristol Myers Squibb Co.

Eli Lilly & Co.

+ [26]

非在研机构

Pfizer Inc.

Merck Healthcare Germany GmbH

Sierra Oncology, Inc.

+ [16]

权益机构

Chosa Oncology AB

Eleison Pharmaceuticals, Inc.

恩康药业科技（广州）有限公司

+ [2]

最高研发阶段批准上市

首次获批日期

美国 (1978-12-19),

膀胱癌卵巢癌睾丸肿瘤

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)、孤儿药 (欧盟)

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结构/序列

分子式Cl2H6N2Pt

InChIKeyWCLAIRSNZFYZAT-UHFFFAOYSA-N

CAS号15663-27-1

关联

4,638

项与顺铂相关的临床试验

NCT07639528

/ Not yet recruiting临床2期IIT

Phase II, Open Label, Non-Randomized, Study of Optimal Preoperative Therapy for Intrahepatic Cholangiocarcinoma (OPTIC)

This phase II trial tests the safety and effectiveness of preoperative immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine with or without futibatinib targeted therapy in treating patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine and/or targeted therapy with futibatinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, rearrangement, or activating mutation, receive immunotherapy, chemotherapy and targeted therapy while patients without a FGFR2 fusion, rearrangement, or activating mutation just receive immunotherapy and chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in patients with resectable intrahepatic cholangiocarcinoma.

开始日期2027-12-10

申办/合作机构

Northwestern University

[+1]

NCT04910386

/ Not yet recruiting临床2期

A Randomized, Open-Label, Multicenter Phase 2 Study of Envafolimab in Combination With Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients With Locally Advanced or Metastatic Biliary Tract Cancers

This is a Randomized, Open-Label, Multicenter Phase 2 Study to access the efficacy and safety of Envafolimab in Combination with Gemcitabine Plus Cisplatin Versus Gemcitabine Plus Cisplatin as the First-line Treatment in Patients with Locally Advanced or Metastatic Biliary Tract Cancers

开始日期2027-06-01

申办/合作机构

四川思路康瑞药业有限公司

NCT04595981

/ Withdrawn临床2期IIT

Chemo-embolization for Head and Neck Cancer

The study will evaluate whether adjuvant chemo-embolization increases progression free and/or overall survival relative to standard of care radiation and chemo- and/or immunotherapy in cisplatin-ineligible head and neck cancer patients with an acceptable morbidity rate.

开始日期2027-05-01

申办/合作机构

The University of Alabama at Birmingham

100 项与顺铂相关的临床结果

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100 项与顺铂相关的转化医学

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100 项与顺铂相关的专利（医药）

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107,203

项与顺铂相关的文献（医药）

2026-12-31·CANCER BIOLOGY & THERAPY

Identification of coilin in bone marrow as a potential neuroblastoma tumor progression marker transcriptionally regulated by MYCN

Article

作者: Zhao, Wen ; Su, Yan ; Gao, Chao ; Cui, Chunying ; Duan, Chao ; Li, Lan ; He, Sidou ; Xue, Tianlin ; Yue, Zhixia ; Liu, Shuguang

BACKGROUND:

Current risk stratification for neuroblastoma (NB) relies on limited markers like MYCN amplification. Coilin, a key Cajal body component, regulates cellular processes. This study investigates whether coilin expression in bone marrow (BM) serves as a predictive biomarker for NB progression and elucidate its function in this disease.

METHODS:

The functions and molecular mechanisms of coilin were investigated by employing cell lines and animal models. Coilin mRNA levels in patient samples were measured by RT-PCR, and their relationships with clinicobiological characteristics and outcomes were analyzed.

RESULTS:

Cisplatin induced dramatic changes of coilin distribution and expression. Databases showed that high expression of coilin exerted predictive values for poor outcome in NB. Coilin promoted proliferation in vitro and in vivo. Knockdown of coilin expression inhibited cell migration and invasion, promoted apoptosis and increased the Cisplatin drug sensitivity. Moreover, coilin activates p53/p21 signaling pathway and was a direct target of MYCN. Analysis of BM samples demonstrated that high expression of coilin was obviously associated with adverse clinical biological features. Importantly, the levels of coilin at diagnosis were markedly higher than those at the time before maintenance treatment in the exact paired patients. Survival analysis presented that high coilin expression in BM is associated with poor prognosis.

CONCLUSIONS:

A novel and accessible coilin-targeted liquid biopsy method was developed, capable of detecting minimal residual disease (MRD) in early-stage NB and predicting disease progression and recurrence. Coilin was transcriptionally regulated by MYCN, offering potential avenues for the development of novel drugs or intervention strategies.

2026-12-31·RENAL FAILURE

Bergamottin pretreatment attenuates cisplatin-induced acute kidney injury in mice by inhibiting BACE-1-mediated ferroptosis

Article

作者: Yuan, Hui-feng ; Wang, Ya-jie ; Peng, Song ; Yang, Xue-ping ; Xu, You-song

Bergamottin is a natural furanocoumarin compound that possesses antioxidative and anticancer properties. However, the effect of bergamottin (BGM) on acute kidney injury (AKI) is unknown. Human renal tubular HK-2 cells and mice that received cisplatin were pretreated with BGM, after which their cytotoxicity and renal function were evaluated. BGM pretreatment alleviated cisplatin-induced cytotoxicity in vitro. Moreover, synergistic protection against cisplatin-induced cytotoxicity was observed when BGM and apoptosis, autophagy, or necrosis inhibitors were used together. There was no synergistic effect between BGM and the ferroptosis inhibitor. Furthermore, BGM significantly inhibited ferroptosis induction-induced damage to HK-2 cells. BGM pretreatment alleviated renal dysfunction and pathological damage by reducing renal proinflammatory cytokines and inhibiting inflammatory cell infiltration, lipid peroxidation and ferroptosis. Based on predictions by SwissTarget and molecular docking, BGM strongly interacts with residues of beta-secretase 1 (BACE-1) via hydrogen and hydrophobic interactions. Moreover, BACE-1 expression was significantly upregulated in the kidneys of AKI mice and HK-2 cells treated with cisplatin but markedly reduced following BGM intervention. Interestingly, siRNA-mediated silencing of BACE-1 in vitro substantially abolished the protective effect of BGM on HK-2 cells that received cisplatin. BGM effectively alleviated AKI by targeting BACE-1 to reduce ferroptosis, suggesting that BGM could be developed as a potential agent for managing and pretreating AKI.

2026-12-31·ANNALS OF MEDICINE

Therapeutic strategies of metabolic reprogramming in non-small cell lung carcinoma

Review

作者: Liu, Jiajun ; Qian, Fenhong

BACKGROUND:

Non-small cell lung carcinoma (NSCLC) remains a leading cause of cancer-related mortality worldwide, with existing therapies frequently hindered by drug resistance and immunosuppression. Metabolic reprogramming (glycolysis, lipid metabolism, and amino acid metabolism) has emerged as a core hallmark driving NSCLC progression, tumor microenvironment (TME) remodeling, and treatment failure, transcending the classical Warburg effect to involve intricate cross-talk between cancer cells and stromal components.

DISCUSSION:

This review systematically synthesizes the latest insights into the regulatory mechanisms of metabolic reprogramming in NSCLC, highlighting how dysregulated glycolytic flux, altered lipid synthesis/oxidation, and adaptive amino acid utilization collectively sustain tumor growth, invasion, and immune escape. We critically examine the interplay between metabolic reprogramming and driver gene mutations (EGFR/KRAS/ALK), unraveling how mutation-specific metabolic adaptations contribute to targeted therapy resistance, and explore the role of metabolic heterogeneity in shaping treatment responses. Furthermore, we dissect actionable therapeutic strategies that target metabolic vulnerabilities, including immunotherapy synergies (e.g. PD-1 inhibitors combined with PKM2/ferroptosis targeting, metabolically modified CAR-T cells), subtype-specific targeted interventions (e.g. DPP4/GFPT2/PFKFB3 inhibitors reversing mutation-driven metabolic resistance), and chemotherapy sensitization approaches (e.g. CPT1A/GLUD1 inhibitors overcoming cisplatin resistance via suppressing metabolic compensation).

CONCLUSION:

This review underscores the clinical potential of targeting metabolic reprogramming to address unmet therapeutic needs, proposing synergistic regimens and personalized metabolic therapy frameworks that hold promise for improving NSCLC patient outcomes.

5,383

项与顺铂相关的新闻（医药）

16 小时之前

·PRNewswire

Intensity Therapeutics Provides Mid-Year Update Highlighting Late-Stage Development Programs and Strategic Partnering Opportunities for INT230-6

Late-stage clinical studies advancing in soft tissue sarcoma and presurgical triple-negative breast cancer Over 200 patients enrolled in completed INT230-6 studies with a peer-reviewed paper published Active strategic partnering initiatives supported by maturing INT230-6 clinical and regulatory profile Strengthened balance sheet supporting disciplined clinical development strategy SHELTON, Conn., July 1, 2026 /PRNewswire/ -- Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of novel intratumoral cancer therapies that are designed to kill tumors and increase immune system recognition of cancers using its proprietary non-covalent conjugation technology, today provides a mid-year update highlighting the Company's late-stage development programs and growing strategic partnering focus for INT230-6. During the first half of 2026, Intensity advanced key clinical and regulatory priorities, strengthened its balance sheet, expanded business development engagement with potential pharmaceutical collaborators and continued building the clinical and scientific foundation for INT230-6 as a differentiated oncology product. "Intensity's human clinical data, peer-reviewed publications, late-stage clinical programs and active regulatory engagement in both the U.S. and Europe have progressed nicely in the past 12 months. Our priority now is to execute and advance our clinical programs, generate meaningful data, publish results, preserve financial flexibility and evaluate partnering opportunities to accelerate development, increase stockholder value and ultimately increase the potential impact of INT230-6 for cancer patients and their caregivers," said Lewis H. Bender, Intensity Therapeutics President and Chief Executive Officer. "We also believe INT230-6 is increasingly positioned as a partnerable oncology platform with potential relevance across difficult-to-treat solid tumors, therapeutic combination-treatment settings, and broader platform-based collaborations." Clinical Progress Across INT230-6 Programs During the first half of 2026, Intensity continued to advance its clinical development priorities across both breast cancer and soft tissue sarcoma. In the Company's Phase 2 INVINCIBLE-4 study in presurgical triple-negative breast cancer ("TNBC"), Intensity reported favorable preliminary observations from a small patient sample evaluating INT230-6 prior to standard-of-care immunochemotherapy compared with standard-of-care therapy alone. The Company previously reported that five of seven patients receiving INT230-6 prior to standard of care achieved a pathological complete response, compared with two of six evaluable patients in the standard-of-care arm, with one patient still to be evaluated. The Company also reported 44% fewer grade 3 or higher adverse events in the INT230-6 cohort compared with the standard-of-care arm. While these observations remain preliminary and from a limited patient population, management believes these observations are important because they support the central clinical thesis of INT230-6: the potential to enhance anti-tumor activity while preserving or potentially improving tolerability when used in combination with existing treatment regimens. In March 2026, a protocol amendment was submitted to Swissmedic and the Swiss Ethics Committee. Full approval to resume enrollment in the INVINCIBLE-4 study was granted on March 26, 2026, and we plan to resume enrollment in the third quarter of 2026 in Switzerland and France as part of its Phase 2/3 development strategy for presurgical TNBC. In soft tissue sarcoma, the Company paused new site activations and patient enrollments in the Phase 3 INVINCIBLE-3 study in March 2025 due to funding constraints. In April 2026, the Company announced it will resume enrollment of the INVINCIBLE-3 study in a limited number of U.S. sites. The INVINCIBLE-3 study is designed to evaluate INT230-6 as monotherapy compared with standard-of-care drugs in second- and third-line treatment for specific soft tissue sarcoma subtypes, with overall survival as the primary endpoint. The decision to resume enrollment in the INVINCIBLE-3 and INVINCIBLE-4 studies reflects management's continued conviction in the scientific rationale and clinical potential of INT230-6 in difficult-to-treat tumors where available treatment options remain limited, and patient outcomes remain poor. Peer-Reviewed Publications Validate Scientific Foundation and Platform Intensity's progress is supported by a clinical foundation that now includes more than 200 patients enrolled across completed INT230-6 studies, including a Phase 1/2 dose escalation study in metastatic cancers and a randomized Phase 2 study in locally advanced breast cancer. The Company previously announced a peer-reviewed publication in eBioMedicine, a Lancet Discovery Science journal, which represented an important validation point for the INT230-6 drug product. The publication reported clinical observations in advanced solid tumors, including evidence of disease control, survival outcomes in certain patient subsets and signs of systemic immune engagement, including observations consistent with abscopal effects in patients receiving higher levels of tumor burden treatment. Management believes this growing body of evidence distinguishes INT230-6 from conventional intratumoral approaches. Rather than relying solely on localized injection effects, Intensity's strategy is designed around the ability to saturate tumors, kill cancer cells, release neoantigens and potentially activate systemic anti-tumor immunity. The Company is seeking to further report clinical data from two completed studies in the second half of 2026 in other peer-reviewed publications. Partnering and Collaborations Initiatives Intensity's recent business development activity reflects growing awareness of INT230-6 among potential pharmaceutical collaborators. At the 2026 BIO International Convention ("BIO") in San Diego, the Company participated in more than 20 partnering discussions, primarily with regionally focused pharmaceutical companies, as well as several global pharmaceutical companies. Management also engaged with companies prior to the BIO conference. Many of these meetings were requested by potential partners, which management believes underscores the strategic relevance of INT230-6 as a differentiated oncology product. While the process is in the early stages, the Company intends to continue actively exploring and evaluating potential partnering and collaboration opportunities that may support the advancement of INT230-6 across priority indications, new indications, geographies, stages of disease and treatment settings, while maintaining disciplined execution and continued data generation with a goal of accelerating long-term stockholder value creation. Strengthened Balance Sheet and Capital Flexibility The Company entered 2026 with cash and cash equivalents of $11.9 million as of December 31, 2025. In March 2026, the Company established a $60 million at-the-market facility and has effectively and opportunistically raised capital during the first half of 2026 to fund operations. As of March 31, 2026, the Company had cash and cash equivalents of $10.2 million. This strengthened financial position is expected to support Intensity's near-term development priorities while providing flexibility as the Company evaluates potential strategic collaborations. Management believes maintaining capital discipline is important to preserving optionality and negotiating from a position of greater strength. About INT230-6 INT230-6, Intensity's lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity's proprietary DfuseRx℠ technology platform. The drug consists of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a diffusion and cell penetration enhancer molecule ("SHAO") that non-covalently conjugates to the two payload drugs, facilitating the dispersion of potent cytotoxic drugs throughout tumors and allowing the active agents to diffuse into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy. About Intensity Therapeutics Intensity is a late-stage clinical biotechnology company whose novel engineered chemistry enables aqueous cytotoxic-containing drug formulations to mix and saturate a tumor's dense, high-fat, pressurized environment following direct intratumoral injection. As a result of the saturation, Intensity's clinical trials have demonstrated the ability of INT230-6 to kill tumors and elicit an adaptive immune response within days of injection, representing a new approach to cancer cell death that holds the potential to shift the treatment paradigm and turn many deadly cancers into chronic diseases even for malignancies that do not respond to conventional immunotherapy. Intensity has completed two clinical studies that enrolled over 200 patients using INT230-6: a Phase 1/2 dose escalation study in metastatic cancers including sarcomas (NCT03058289), and a Phase 2 randomized control clinical trial in locally advanced breast cancer (the "INVINCIBLE-2 Study") (NCT04781725) in women without undergoing chemotherapy prior to their surgery. The Company initiated a Phase 3 trial in soft tissue sarcoma (the "INVINCIBLE-3 Study") (NCT06263231), testing INT230-6 as second or third-line monotherapy compared to the SOC with overall survival as an endpoint. Intensity also initiated a Phase 2 study in collaboration with the Swiss Cancer Institute (the "INVINCIBLE-4 Study") (NCT06358573) as part of a Phase 2/3 program evaluating INT230-6 followed by the SOC immunochemotherapy and the SOC alone for patients with presurgical triple-negative breast cancer. pCR is the endpoint. For more information about Intensity, including publications, papers, and posters about its novel approach to cancer therapeutics, visit or review our SEC filings. Forward-Looking Statements Certain statements in this press release may constitute "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995, as amended to date. These statements include, but are not limited to, statements relating to the Company's expected future plans, cash runway, development activities, projected milestones, business activities or results. When or if used in this communication, the words "may," "could," "should," "anticipate," "believe," "estimate," "expect," "intend," "plan," "predict" and similar expressions and their variants, as they relate to the Company or its management, may identify forward-looking statements. The forward-looking statements contained in this press release are based on management's current expectations and projections about future events. Nevertheless, actual results or events could differ materially from the plans, intentions, and expectations disclosed in, or implied by, the forward-looking statements. These risks and uncertainties, many of which are beyond our control, include: the initiation, timing, progress and results of future preclinical studies and clinical trials and research and development programs; the need to raise additional funding before the Company can expect to generate any revenues from product sales; plans to develop and commercialize product candidates; the timing or likelihood of regulatory filings and approvals; the ability of the Company's research to generate and advance additional product candidates; the risk that product candidates that appear promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials; the implementation of the Company's business model, strategic plans for the Company's business, product candidates and technology; commercialization, marketing and manufacturing capabilities and strategy; the rate and degree of market acceptance and clinical utility of the Company's system; the Company's competitive position; the Company's intellectual property position; developments and projections relating to the Company's competitors and its industry; the Company's ability to maintain and establish collaborations or obtain additional funding; expectations related to the use of cash and cash equivalents and investments; our potential inability to satisfy the Nasdaq Capital Market's requirements for continued listing and be subject to delisting; estimates regarding expenses, future revenue, capital requirements and needs for additional financing; and other risks described in the section entitled "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2025 and in the Company's subsequent SEC ﬁlings, which can be obtained on the SEC website at . Readers are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date on which they are made and reflect management's current estimates, projections, expectations and beliefs. The Company does not plan to update any such forward-looking statements and expressly disclaims any duty to update the information contained in this press release except as required by law. Investor Relations Contact: Justin Kulik CORE IR [email protected] (516) 222-2560 Media Contact: Matt Cossel CORE IR [email protected] SOURCE Intensity Therapeutics Inc. 21% more press release views with Request a Demo

临床2期免疫疗法临床结果临床3期

17 小时之前

·药学进展

独家原创 | 骨肉瘤肿瘤干细胞的调控机制与相关治疗策略研究进展

“ 点击蓝字关注我们骨肉瘤肿瘤干细胞的调控机制与相关治疗策略研究进展 PPS 王霞 1 ，张晓鲁 2* （1. 山东大学齐鲁医院骨科，山东济南 250012；2. 山东大学基础医学院病理生理教研室，山东济南 250012）张晓鲁山东大学基础医学院病理生理学系主任，教授，博士生导师。山东大学齐鲁青年学者，山东省泰山学者青年专家。曾在瑞典卡罗林斯卡医学院获肿瘤学博士学位。主要研究方向为肿瘤异质性及肿瘤克隆进化，近5年以通信作者身份在Hepatology、Cell Rep Med、Biomark Res、Nucleic Acids Res、 CMGH、Nat Commun等国际高水平期刊发表SCI论文数篇。主持国家自然科学基金项目、山东省自然科学基金项目，承担科技部重点研发计划青年科学家项目。担任中国抗癌协会肿瘤分子医学专业委员会常务委员、山东省病理生理学会常任理事，山东省病理生理学会青年专业委员会副主任委员等，参编人民卫生出版社“十四五”规划教材《病理生理学》（第10版）、人民卫生出版社《医学大数据技术》（第1版）、科学出版社“十四五”规划第4轮教材《病理生理学》等多部全国高等学校本科临床医学专业教材。 [摘要] 骨肉瘤是常见的原发性恶性骨肿瘤之一，主要发生于儿童和青少年。尽管手术联合化疗等综合治疗在局部控制方面取得一定进展，但转移性和复发性骨肉瘤的预后仍不理想。近年来，肿瘤干细胞（cancer stem cell，CSC）被认为在骨肉瘤的发生、进展、耐药及转移过程中发挥关键作用，成为研究热点。系统综述了骨肉瘤中CSC的生物学特性、关键分子标志物、信号通路调控机制及其与肿瘤微环境的相互作用，并探讨其作为临床治疗潜在靶点的转化价值，旨在为骨肉瘤的精准治疗提供理论依据和研究方向。骨肉瘤（osteosarcoma）是一种起源于间充质成骨细胞的高度恶性骨肿瘤，好发于青少年，发病高峰集中在10至20岁之间[1-2]。常见于长骨干骺端，尤其是股骨远端、胫骨近端和肱骨近端。临床表现为局部疼痛、肿胀、功能障碍，晚期可出现病理性骨折及远处转移，其中肺转移最为常见且显著影响预后。随着新辅助化疗和保肢手术的发展，局部病灶控制率明显提高，5年总生存率可达60%~70%。然而，对于存在肺转移、术后复发或对化疗不敏感的患者，预后仍然较差。传统治疗主要针对增殖活跃的肿瘤细胞，而对具有自我更新和多向分化潜能的肿瘤干细胞（cancer stem cell，CSC）则疗效有限[3]。 CSC理论最初源于白血病干细胞的研究。近年来，大量证据表明，在乳腺癌、肝癌、脑胶质瘤等多种实体瘤中均存在CSC亚群，其在肿瘤发生、侵袭、转移、耐药和复发中起“种子”作用[1]。在骨肉瘤中亦已鉴定出多个CSC相关表型，包括分化簇（cluster of differentiation，CD）133、醛脱氢酶1（aldehyde dehydrogenase 1，ALDH 1）、基质细胞抗原1（stromal cell antigen 1，Stro-1）、CD 117、CD271、巢蛋白（Nestin）等标志物。这些CSC亚群通常表现出强增殖能力、化疗耐受性以及肺转移倾向。值得注意的是，CSC并非孤立存在于肿瘤组织中，其干性维持与功能激活高度依赖于复杂的内外部调控网络：内部依赖Wnt/β-连环蛋白(β -catenin）、Notch、Hedgehog及磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）等信号通路的协同作用，外部则受到肿瘤微环境（tumor microenvironment，TME）的显著调控[4]。TME中的免疫抑制细胞、肿瘤相关成纤维细胞（cancer-associated fibroblast，CAF）、血管内皮细胞及缺氧等关键因素可通过多种机制调节CSC的干性，影响其增殖、迁移及免疫逃逸能力[5]。因此，靶向CSC被认为是改善骨肉瘤临床预后的潜在策略。基于此，本文整合近年来国内外研究成果，从CSC的表型识别、功能特征、信号通路调控、微环境互作及临床转化等多个层面进行系统综述，并重点突出以下三方面内容：第一，以“临床转化”为核心主线，系统整合CSC从基础机制到靶向治疗策略的完整转化链条，强化基础研究与临床应用的衔接；第二，重点解析TME与CSC互作的调控网络，阐释二者双向调控的分子机制，凸显微环境在干性维持及治疗抵抗中的关键作用；第三，融入单细胞RNA测序、成簇规律间隔短回文重复序列（clustered regularly interspaced short palindromic repeats，CRISPR）-CRISPR关联蛋白9（CRISPR-associated protein 9，Cas9）基因编辑系统等前沿技术在CSC研究中的应用进展，为骨肉瘤精准靶向干预方案的设计提供新视角。 1 骨肉瘤的基本特征 1.1 流行病学特征骨肉瘤是一种罕见但高度恶性的原发性骨肿瘤，全球年发病率约为每百万人2~3例。在中国，该病在15岁以下儿童和青少年中相对高发[6]。发病呈单峰分布，青春期为发病高峰，提示其与骨骼快速生长密切相关。男性发病率略高于女性[7]。 1.2 临床表现与影像学特征骨肉瘤患者常以进行性局部疼痛为首发症状，伴随肿胀、局部皮温升高或活动受限，少数因病理性骨折首次就诊。影像学上表现为溶骨性破坏与新生骨形成并存，典型X线征象包括“日光放射样”、骨膜反应和Codman三角。磁共振成像（magnetic resonance imaging，MRI）有助于评估肿瘤边界及软组织侵犯范围，胸部计算机断层扫描（computed tomography，CT）为肺转移筛查的首选方法。 1.3 组织病理与分子特征组织学上，骨肉瘤根据基质分化可分为成骨型、软骨型和纤维型，其中以成骨型最常见。常用免疫组化标记物包括SATB2、骨钙素（osteocalcin）和Runt相关转录因子2（Runt-related transcription factor 2，Runx2）。分子水平上，骨肉瘤具有高度基因组不稳定性，常见突变涉及TP53、RB1、CDKN2A和PTEN等基因。近年研究表明，PI3K/AKT、Wnt/β-catenin和丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等信号通路的异常激活与其恶性行为密切相关。 1.4 标准治疗与预后目前骨肉瘤的标准治疗采用术前新辅助化疗、广泛切除手术及术后辅助化疗的多模式方案。常用化疗药物包括高剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）、阿霉素（doxorubicin，ADM）、顺铂（cisplatin，DDP）和异环磷酰胺（ifosfamide， IFO）[8-9]。随着保肢技术的进步，超过80%的患者可接受保肢手术。但对于伴有肺转移、初治化疗不敏感或复发的患者，5年生存率低于30%。表1总结了不同病情骨肉瘤患者的预后差异及影响因素。新型靶向治疗与免疫治疗正处于临床试验探索阶段，CSC被视为未来突破的关键靶点之一。 2 骨肉瘤肿瘤干细胞的识别与功能验证 2.1 肿瘤干细胞的定义与功能 CSC是指具有自我更新能力、无限增殖潜能及多向分化特性的肿瘤细胞亚群，可在体内或体外重建异质性肿瘤群体。此类细胞通常对常规化疗和放疗具有较强耐受性，被认为是导致肿瘤复发和转移的根本原因[10]。 2.2 表面标志物的识别在骨肉瘤中，常见的CSC相关标志物包括CD 133、CD 117、Stro-1、CD271、ALDH 1A 1和Nestin等[11-12]。CD 133+细胞表现出更强的球体形成能力、侵袭迁移能力和化疗抵抗性。ALDH 1活性常用于富集干细胞样细胞，其高表达与不良预后显著相关。Stro-1被认为是间充质干细胞样CSC的标志物之一[13]。 2.3 功能验证手段骨肉瘤CSC的功能验证主要依赖以下模型。1）成球实验：CSC可在无血清悬浮条件下形成三维肿瘤球体；2）体内异种移植模型：CSC富集群体在免疫缺陷小鼠中表现出更高的致瘤能力；3）化疗耐药模型：CD 133+细胞在暴露于顺铂、阿霉素等药物后仍保持较高存活率，提示其为化疗后残留细胞的核心组成部分[14-15]。 2.4 干性维持机制骨肉瘤CSC的干性维持受多种内在转录因子[如八聚体结合转录因子4（octamer-binding transcription factor 4，OCT4）、性别决定区Y框蛋白2（sex-determining region Y-box 2，SOX2）、Nanog同源盒（Nanog homeobox，NANOG）]和外源性信号通路共同调控。OCT4/NANOG的高表达常与肿瘤高级别及转移潜能相关[16]。此外，miRNA调控网络（如miR-34a、miR-145）在CSC状态维持中亦发挥重要作用。表2总结了骨肉瘤CSC核心标志物的功能特征及临床关联。 3 调控骨肉瘤肿瘤干细胞的信号通路 CSC的维持与激活涉及多个关键信号通路，这些通路通过调节CSC的增殖、自我更新、抗凋亡及侵袭转移等过程，深刻影响骨肉瘤的恶性表型（见图1）。 3.1 Wnt/β-catenin信号通路 Wnt信号通路在干细胞稳态维持和组织发育中具有重要作用。在骨肉瘤中，活化的Wnt/β-catenin通路可增强CSC的干性特征、化疗耐受性及迁移能力[17]。β-catenin在细胞核内的积聚是该通路激活的重要标志，可促进OCT4、SOX2等干性相关转录因子的表达。研究显示，Wnt通路的上游配体（如Wnt3a）和下游效应分子[如细胞周期蛋白D1（Cyclin D1）、c-Myc]在CD133+骨肉瘤细胞中显著上调，提示其在CSC干性特征维持中发挥核心作用[18-19]。 3.2 Notch信号通路 Notch通路通过细胞间直接接触介导信号传递，参与干细胞命运决定和组织稳态调控[20]。该通路在骨肉瘤CSC中呈活化状态，Notch1及其配体Jagged1表达上调，进而诱导Hes1、Hey1等靶基因表达，维持CSC的未分化状态和耐药特性[21]。γ-分泌酶抑制剂如N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰基]-S-苯基甘氨酸叔丁酯（N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester，DAPT）已在体外研究中被证实可有效抑制骨肉瘤CSC的球体形成和迁移能力，提示Notch通路抑制剂具有潜在治疗价值[22]。 3.3 Hedgehog信号通路 Hedgehog信号通路是胚胎发育的重要调控通路，在骨肉瘤CSC中亦被广泛激活。其激活机制为配体Shh（Sonic Hedgehog）与受体Ptch结合，解除对SMO的抑制，从而激活GLI家族锌指蛋白1/2（GLI family zinc finger 1/2，GLI 1/2）介导的转录程序[23]。GLI1的高表达与骨肉瘤不良预后密切相关[24-25]。 3.4 基质细胞与细胞外基质相关的信号通路 CAF通过分泌白细胞介素（interleukin，IL）-6、C-X-C基序趋化因子配体12（C-X-C motif chemokine ligand 12，CXCL 12）、基质金属蛋白酶（matrix metalloproteinase，MMP）等因子重塑细胞外基质（extracellular matrix，ECM）[26]，并与CSC形成相互依赖的信号反馈回路，促进其干性维持及侵袭能力。此外，ECM中的胶原蛋白Ⅰ、纤维连接蛋白和透明质酸可激活整合素/黏着斑激酶（focal adhesion kinase，FAK）/Src激酶（Src kinase，Src）等信号通路，增强CSC的黏附性、迁移能力和耐药性[27]。 3.5 血管生态位相关的信号通路 CSC倾向于在肿瘤血管周围聚集，形成“血管生态位”。内皮细胞可通过释放一氧化氮（nitric oxide，NO）、血管生成素-1/2（angiopoietin-1/2，Ang-1/2）和血管内皮生长因子（vascular endothelial growth factor，VEGF）等因子支持CSC的自我更新与存活[28]。异常的肿瘤血管结构在提供氧气和营养的同时，亦为CSC进入循环系统创造了条件，促进远处转移灶的形成。总之，TME作为维持CSC干性的外部调控网络，在介导治疗抵抗和肿瘤复发的过程中发挥关键作用（见图2）。靶向TME与CSC之间的相互作用机制，已成为实现肿瘤根除的重要策略之一[29]。 4 肿瘤干细胞的临床转化与靶向治疗策略随着对骨肉瘤CSC生物学特性的深入理解，其作为潜在治疗靶点的价值日益受到关注。近年来，多种靶向CSC的治疗策略相继提出，部分已进入临床前或早期临床试验阶段，展现出良好的应用前景。 4.1 肿瘤干细胞相关标志物的预后价值临床研究表明，骨肉瘤组织中CD 133、ALDH 1、Stro-1等CSC标志物的高表达与患者较差的无病生存期（disease-free survival，DFS）和总生存期（overall survival，OS）显著相关[30]。通过免疫组织化学或流式细胞术检测这些标志物，有助于实现患者的危险分层和预后评估。此外，外周血中循环肿瘤干细胞（circulating tumor stem cell，CTSC）的检出与肿瘤转移趋势密切相关，为疾病进展的动态监测提供了新的液体活检思路。相较于传统组织活检，液体活检具有微创、可重复采样、实时反映全身肿瘤负荷等优势，在复发转移预警、治疗效果评估中展现出潜在应用价值。然而，这类标志物向临床常规应用转化时仍面临诸多技术瓶颈：其一，检测灵敏度不足，早期骨肉瘤患者外周血中CTSC数量稀少，常处于“稀有细胞”水平，易被大量正常血细胞干扰，现有富集与检测技术难以高效捕获并精准识别；其二，特异性有限，CD 133、ALDH 1等标志物并非骨肉瘤CSC特有，在部分正常干细胞或其他肿瘤类型中可能存在低表达，易导致假阳性结果，影响评估准确性；其三，缺乏标准化检测流程，不同研究采用的样本处理方法、抗体选择及检测平台[流式细胞术、聚合酶链反应（polymerase chain reaction，PCR）等]存在差异，临界值判定标准不统一，导致检测结果的可比性和重复性较差；其四，标志物异质性挑战，骨肉瘤CSC群体具有高度异质性，单一标志物检测易遗漏部分干性亚群，而多标志物联合检测虽能提升准确性，但会增加技术复杂度和临床应用成本，限制其普及推广。这些问题需通过优化富集策略、开发高特异性检测工具、建立统一标准等方式逐步解决，以充分发挥CSC相关标志物在预后评估与动态监测中的临床价值。 4.2 靶向肿瘤干细胞的治疗策略基于骨肉瘤CSC的生物学特性及调控机制，目前已开发出多种针对性靶向治疗策略，涵盖信号通路抑制、特异性免疫治疗、分化诱导及联合治疗等多个方向，表3对各类策略的核心机制、代表药物/治疗技术进行了汇总。 4.2.1 信号通路抑制剂针对Wnt、Notch、Hedgehog、PI3K/AKT等关键信号通路的抑制剂正在广泛研究中。例如，ICG-001通过阻断β-catenin/CREB结合蛋白（CREB-binding protein，CBP）结合抑制干性基因表达[31]；γ-分泌酶抑制剂DAPT可抑制Notch通路活化，削弱CSC的未分化状态与耐药性；GANT61可通过抑制Hedgehog通路中GLI转录因子活性降低CSC的致瘤性。PI3K/AKT通路抑制剂LY294002可通过阻断下游信号传导，抑制CSC增殖与迁移。多数在体外及动物模型中的研究显示，这类抑制剂可有效抑制CSC增殖、削弱干性特征并提高肿瘤细胞对顺铂、阿霉素等化疗药物的敏感性。从临床进展来看，部分药物已进入早期临床试验阶段：Wnt通路抑制剂LGK974处于实体瘤Ⅰ期临床试验（NCT01351103）阶段，Hedgehog通路抑制剂LY3039478已推进至实体瘤聂期临床试验（NCT02071861），但专门针对骨肉瘤的特异性临床试验数据仍较为匮乏。其局限性主要体现在三方面：一是单一通路抑制易诱发代偿性激活，如阻断Wnt通路后可能导致PI3K/AKT通路异常活化，影响治疗效果；二是脱靶毒性明显，多数信号通路在正常干细胞及组织稳态中也发挥作用，全身给药可能损伤正常组织功能；三是肿瘤异质性导致部分患者对抑制剂不敏感。基于此，联合用药成为重要研发方向，如PI3K/AKT抑制剂与Wnt抑制剂联合使用，可通过协同阻断多干性通路，提升对CSC的清除效率，同时降低单一药物的使用剂量，减少毒性反应。 4.2.2 肿瘤干细胞特异性免疫治疗该策略利用CSC表面特异性抗原，通过免疫手段精准杀伤CSC，主要包括嵌合抗原受体T细胞（chimeric antigen receptor T cell，CAR-T）技术与CSC相关抗原疫苗两大类。其中CAR-T技术以CD 133、人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）等CSC相关抗原为靶点，在复发/转移性骨肉瘤Ⅰ期临床试验[如抗CD 133 CAR-T的试验（NCT04580486）、抗HER2 CAR-T的试验（NCT02159717）]中初步展现出抗肿瘤潜力，未观察到严重脱靶毒性，但部分患者因CSC下调靶抗原表达出现治疗耐药。CSC相关抗原疫苗（如CD 133多肽疫苗）则通过诱导机体产生特异性CD8+T细胞应答，在骨肉瘤动物模型中显著抑制CSC致瘤性，目前仍处于临床前研究阶段，核心研发方向为优化疫苗佐剂以提升免疫原性与持久免疫应答。该类治疗的主要局限性包括：TME的免疫抑制作用会削弱CAR-T细胞浸润与杀伤功能，降低治疗效果；CSC群体的抗原异质性易导致抗原逃逸，单一靶点治疗难以覆盖所有干性亚群；CAR-T制备成本高、流程复杂，限制了其普及应用。联合免疫检查点抑制剂[如程序性死亡受体1（programmed cell death protein 1，PD-1）抗体]可有效逆转TME免疫抑制，增强CAR-T或疫苗诱导的抗CSC免疫效应，已成为该领域的重要研发趋势；此外，双靶点（如CD 133/CD271双靶点）CAR-T的开发，可降低抗原逃逸风险，进一步提升治疗特异性与有效性。 4.2.3 分化诱导治疗诱导CSC向终末分化方向转化，使其丧失干性特征与耐药性，是一种低毒性的治疗策略。维甲酸类药物如全反式维甲酸（all-trans retinoic acid，ATRA）、其衍生物他米巴罗汀（tamibarotene，AM80）可通过结合维甲酸受体（retinoic acid receptor，RAR），促使CSC丧失自我更新能力，降低其致瘤潜能，其中ATRA联合化疗的聂期临床试验（NCT00003092）显示可轻度提升骨肉瘤患者PFS，但疗效存在明显个体差异；组蛋白去乙酰化酶（histone deacetylase，HDAC）抑制剂（如伏立诺他、西达本胺）可通过表观遗传调控破坏CSC干性维持网络，伏立诺他处于Ⅰ期临床试验阶段，西达本胺正在探索骨肉瘤适应证（聂期），且研究证实西达本胺可与ATRA协同诱导骨肉瘤CSC分化，提升治疗效果[32]；此外，zeste基因增强子同源物2（enhancer of zeste homolog 2，EZH2）抑制剂EPZ-6438等新型分化诱导剂也处于临床前研究阶段，展现出良好的应用潜力。该策略的优势在于治疗方式温和，脱靶毒性低，可与化疗协同清除分化后肿瘤细胞，但也存在明显局限性：部分CSC因缺乏相应受体（如RAR）对诱导药物不敏感，且分化诱导可能导致部分CSC进入暂时休眠状态，而非彻底清除，为肿瘤复发留下隐患。未来研发重点将聚焦于高效分化诱导剂的筛选，以及其与信号通路抑制剂、化疗药物的联合应用，通过“诱导分化+杀伤”的协同作用，提升对CSC的清除效率。 4.2.4 联合治疗策略鉴于单一靶向CSC难以实现彻底清除干性亚群，且易诱发耐药，联合治疗已成为主流研发方向，核心思路为整合不同策略的作用机制，实现对CSC的高效清除。目前研究较为成熟的联合方案包括：1）信号通路抑制剂与化疗联用。例如，Wnt抑制剂ICG-001联合顺铂的聂期临床试验（NCT05123456）初步结果显示，该治疗方案可将复发/转移性骨肉瘤患者的客观缓解率提升至35%，显著高于顺铂单药治疗（18%），其优势在于先通过抑制剂削弱CSC干性，增强骨肉瘤CSC对化疗的敏感性，再以化疗清除分化后的肿瘤细胞，减少耐药残留[31]；2）CAR-T与免疫检查点抑制剂联用。通过PD-1抗体逆转TME免疫抑制，增强CAR-T对CSC的浸润与杀伤功能，在骨肉瘤Ⅰ期临床试验中已观察到部分患者肿瘤缩小。3）分化诱导剂与信号通路抑制剂联用。如ATRA+GANT61，通过协同破坏骨肉瘤CSC干性维持的内在调控网络，提升分化诱导效果，目前处于临床前优化阶段。联合治疗的核心优势在于可协同增效，克服单一治疗的耐药问题，覆盖CSC多调控环节，实现更彻底的肿瘤清除，但也面临用药剂量与时序优化、不良反应叠加、部分联合机制不明确等挑战。未来需通过临床前研究明确不同药物的协同作用机制，再通过临床试验优化联合方案的给药顺序与剂量，以在提升疗效的同时控制不良反应。 4.3 前沿研究与技术支持单细胞RNA测序、空间转录组学、基因编辑技术（如CRISPR-Cas9）的快速发展[33]，为识别CSC特异性分子标记、解析其转录图谱及空间分布提供了强有力的技术支撑。例如，单细胞测序可揭示CSC亚群的演化轨迹及其与TME的交互机制，进而指导更精准的靶向干预方案设计。 5 结语与展望尽管骨肉瘤CSC研究已取得重要进展，但在基础研究、临床应用与转化医学层面仍面临诸多挑战，亟需进一步探索与突破。首先，CSC标志物存在明显的异质性且缺乏统一标准。当前用于鉴定CSC的标志物多来源于不同实验体系，存在明显的模型依赖性和组织特异性差异。尽管CD 133、ALDH 1、Stro-1等标志物被广泛应用，但其特异性和稳定性尚存争议，各研究间对CSC亚群的定义缺乏共识。这种异质性严重限制了研究结果的可比性，也阻碍了CSC靶向疗法的临床推广。其次，体外培养模型存在局限性。现有CSC研究主要依赖于体外球体培养和动物异种移植模型，难以真实再现TME中CSC的生理状态及其动态演变过程。缺乏高保真、可重复的模型体系，制约了功能研究的深度以及新药筛选的临床转化潜力。再者，CSC靶向治疗的安全性与有效性问题值得关注。尽管多种靶向CSC的策略在实验阶段表现良好，但其临床疗效和安全性尚未充分验证。部分CSC标志物在正常干细胞中亦有表达，靶向干预可能导致组织毒性或不可逆损伤。此外，单一通路抑制常难以彻底清除CSC，耐药性发展和代偿性信号通路激活仍是临床应用中的主要障碍。同时，多组学与系统生物学研究也亟待加强。目前对CSC的认识多局限于分子或细胞水平，缺乏系统整合的生物信息学分析。未来需加强转录组、表观遗传组、代谢组及空间组学的多维度协同研究，构建CSC动态调控网络与演化路径图谱，为识别关键调控节点和治疗窗口提供理论依据。展望未来，相关研究应聚焦以下几个方向：1）建立标准化的CSC检测与功能验证体系，推动其在临床的常规化应用；2）开发高选择性CSC靶向药物，最大限度减少对正常干细胞的影响；3）深入探究CSC与免疫系统、肿瘤代谢之间的相互作用，推进免疫联合治疗策略的发展；4）强化跨学科协作，整合临床样本队列、大数据挖掘与人工智能技术，助力CSC识别与干预方案的优化。 CSC作为导致骨肉瘤生物学异质性和临床治疗失败的核心因素，正逐步成为肿瘤研究的重点领域。通过深入阐明其分子机制、调控网络及微环境依赖特性，有望为骨肉瘤的早期诊断、精准治疗和复发预防提供革新性策略。尽管面临诸多挑战，随着基础研究与临床转化的持续推进，靶向CSC的治疗手段有望成为攻克骨肉瘤的关键突破口。参考文献： [1] Yu S, Yao X. 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Sig Transduct Target Ther, 2021, 6: 307. [20] Zhu L, McManus M M, Hughes D P. Understanding the biology of bone sarcoma from early initiating events through late events in metastasis and disease progression[J]. Front Oncol, 2013, 3: 230. [21] Moore G, Annett S, McClements L, et al. Top Notch targeting strategies in cancer: a detailed overview of recent insights and current perspectives[J]. Cells, 2020, 9(6): 1503. [22] 张浩 . 骨肉瘤分子分型及各亚型肿瘤学性质表征 [D]. 上海 :中国人民解放军海军军医大学, 2021: 39-49. [23] Banaszek N, Kurpiewska D, Kozak K, et al. Hedgehog pathway in sarcoma: from preclinical mechanism to clinical application[J]. J Cancer Res Clin Oncol, 2023, 149(19): 17635-17649. [24] Cheng D D, Li J, Li S J, et al. CNOT 1 cooperates with LMNAto aggravate osteosarcoma tumorigenesis through the Hedgehog signaling pathway[J]. Mol Oncol, 2017, 11(4): 388-404. [25] Jeng K S, Sheen I S, Leu C M, et al. The role of smoothened in cancer[J]. Int J Mol Sci, 2020, 21(18): 6863. [26] de Visser K E, Joyce J A. The evolving tumor micro- environment: from cancer initiation to metastatic outgrowth[J].Cancer Cell, 2023, 41(3): 374-403. [27] van Niel G, Carter D R F, Clayton A, et al. Challenges and directions in studying cell-cell communication by extracellular vesicles[J]. Nat Rev Mol Cell Biol, 2022, 23(5): 369-382. [28] Kim W, Park A, Jang H H, et al. Breast tumor cell-stimulated bone marrow-derived mesenchymal stem cells promote the sprouting capacity of endothelial cells by promoting VEGF expression, mediated in part through HIF-1α increase[J]. Cancers, 2022, 14(19): 4711. [29] Trivanović D, Krstić J, Djordjević I O, et al. The roles of mesenchymal stromal/stem cells in tumor microenvironment associated with inflammation[J]. Mediat Inflamm, 2016, 2016: 7314016. [30] Han Y, Sun B, Cai H, et al. Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti- CD 133 CAR-T combination therapy[J]. Cancer Immunol Immunother, 2021, 70(10): 2795-2803. [31] Choi J H, Jang T Y, Jeon S E, et al. The small-molecule Wnt inhibitor ICG-001 efficiently inhibits colorectal cancer stemness and metastasis by suppressing MEIS 1 expression[J]. Int J Mol Sci, 2021, 22(24): 13413. [32] Irimia R, Piccaluga P P. Histone deacetylase inhibitors for peripheral T-cell lymphomas[J]. Cancers, 2024, 16(19): 3359. [33] Dimitri A, Herbst F, Fraietta J A. Engineering the next- generation of CAR T-cells with CRISPR-Cas9 gene editing[J]. Mol Cancer, 2022, 21(1): 78. 本文引文格式：王霞, 张晓鲁. 骨肉瘤肿瘤干细胞的调控机制与相关治疗策略研究进展[J]. 药学进展, 2026, 50(3): 219-226. 美编排版：王子怡感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2026年第 3 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.311，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“第七届药学前沿学术论坛暨《药学进展》编委会会议” 聚力前沿赛道，共启学术新程：第七届药学前沿学术论坛在南京隆重启幕承学术匠心，启时代新章：《药学进展》第七届编委会、第三届青年编委会成立大会在宁召开聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

2026-06-30

·生物药观察

康方启动AK146D1+AK112的第2项临床2期研究

IO2.0+ADC2.0已经成为康方产品开发的重要战略。继2026年5月中旬启动AK146D1（TROP2/Nectin-4 双抗ADC）联合依沃西单抗（PD-1/VEGF）在乳腺癌的的临床II期研究（NCT07591090，AK146D1-202）后（康方生物连续启动IO2.0+ADC2.0的临床研究），康方生物于2026年6月25日，在clinicaltrail登记了AK146D1联合依沃西单抗的第2项联用临床研究（NCT07669779，CTR20262393，AK146D1-201），适应症为晚期非小细胞肺癌。研究预计在中国大陆纳入348例晚期非小细胞肺癌受试者，评估AK146D1联合AK112和卡铂/顺铂或奥希替尼的安全性、耐受性和抗肿瘤活性。中山大学肿瘤防治中心张力教授和徐瑞华教授为主要研究者。附表更新：IO2.0代表性产品PD-(L)1/VEGF联用ADC的研究进展

100 项与顺铂相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00275	顺铂	L01XA01	DB00515

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
胆道癌	日本	Nippon Kayaku Co., Ltd.	2012-02-22
头颈部鳞状细胞癌	巴西	Libbs Farmacêutica Ltda.	2007-01-22
恶性胸膜间皮瘤	日本	Nippon Kayaku Co., Ltd.	2007-01-04
儿童恶性实体瘤	日本	Nippon Kayaku Co., Ltd.	2005-09-15
淋巴瘤	日本	Nippon Kayaku Co., Ltd.	2005-09-15
骨癌	日本	Nippon Kayaku Co., Ltd.	2005-02-14
子宫内膜癌	日本	Nippon Kayaku Co., Ltd.	2005-02-14
生殖细胞瘤	日本	Nippon Kayaku Co., Ltd.	2004-05-31
肝细胞癌	日本	Nippon Kayaku Co., Ltd.	2004-01-29
骨肉瘤	日本	Nippon Kayaku Co., Ltd.	1999-12-21
小细胞肺癌	日本	Nippon Kayaku Co., Ltd.	1999-12-21
实体瘤	中国	德州博诚医药科技有限公司	1995-01-01
实体瘤	中国	德州德药制药有限公司	1995-01-01
实体瘤	中国	云南植物药业有限公司	1995-01-01
实体瘤	中国	昆明贵研药业有限公司	1995-01-01
实体瘤	中国	齐鲁制药有限公司	1995-01-01
胃癌	日本	Nippon Kayaku Co., Ltd.	1990-06-03
食管癌	日本	Nippon Kayaku Co., Ltd.	1988-05-30
神经母细胞瘤	日本	Nippon Kayaku Co., Ltd.	1988-05-30
宫颈癌	日本	Nippon Kayaku Co., Ltd.	1988-05-30

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
肌层浸润性膀胱癌	临床3期	澳大利亚	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	巴西	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	加拿大	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	法国	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	意大利	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	荷兰	AstraZeneca PLC	2025-05-15
肌层浸润性膀胱癌	临床3期	西班牙	AstraZeneca PLC	2025-05-15
口腔鳞状细胞癌	临床3期	美国	Privo Technologies, Inc.	2024-11-07
输卵管癌	临床3期	美国	GSK Plc	2024-03-08
原发性腹膜癌	临床3期	美国	GSK Plc	2024-03-08

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


JPRN-UMIN000051689 (ASCO2026)	临床3期	不能切除的胆道癌一线	460	gemcitabine + cisplatin + S-1	繭鏇鹽夢積鏇網繭蓋簾(鹹憲憲淵築遞艱鹹艱淵) = 築艱網構夢廠鬱廠鏇艱膚範遞積窪網鏇憲鑰繭 (願齋膚壓觸窪願壓觸襯 )	积极	2026-05-29
NCT06423326 (ASCO2026)	临床2期	胰腺导管腺癌新辅助	12	Gemcitabine, Cisplatin, and Nab-paclitaxel	繭築醖鏇顧顧選顧鹹窪(繭網範窪廠糧夢艱膚獵) = 鏇網淵廠選選鬱鏇艱鬱醖獵衊窪製壓觸鹽製夢 (範衊鏇獵遞獵鏇顧網艱 ) 更多	积极	2026-05-29
ASCO2026	N/A	头颈部鳞状细胞癌	59	Docetaxel, cisplatin, and oral tegafur-uracil (DCU)	鏇襯衊壓艱選憲觸淵顧(艱鬱膚餘鹽鏇鏇鑰範糧) = higher proportion of patients treated with PDCU 鹹壓夢顧鑰憲選艱網願 (壓鹹選繭製顧膚醖壓製 )	积极	2026-05-29
ASCO2026	N/A	头颈部鳞状细胞癌	59	Pembrolizumab plus DCU (PDCU)		积极	2026-05-29
ASCO2026	N/A	头颈部鳞状细胞癌新辅助	101	tislelizumab+albumin-bound paclitaxel+ cisplatin	觸淵艱鏇糧鏇夢襯構選(淵鬱範網蓋遞糧壓鏇鹽) = 觸糧壓壓窪鹹淵構選艱構築繭夢選艱製鏇獵簾 (遞願網壓範網廠醖鬱糧 ) 更多	积极	2026-05-29
ASCO2026	N/A	胰腺癌一线	138	PAXG (cisplatin, nab-paclitaxel, capecitabine and gemcitabine)	淵醖憲觸簾網築齋範範(衊顧憲鹹構鹹鬱鏇製蓋) = 簾積憲鑰願觸網齋憲觸衊繭窪膚選顧繭醖鏇窪 (繭蓋窪糧襯範壓衊鏇廠 ) 更多	积极	2026-05-29
ASCO2026	N/A	胰腺癌一线	138	mFOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin)	淵醖憲觸簾網築齋範範(衊顧憲鹹構鹹鬱鏇製蓋) = 襯鹹網窪淵繭範餘廠選衊繭窪膚選顧繭醖鏇窪 (繭蓋窪糧襯範壓衊鏇廠 ) 更多	积极	2026-05-29
NCT01970722 (ASCO2026)	临床1期	卵巢癌	41	Cisplatin 75 mg/m2 (good responder)	簾衊鑰獵獵鑰廠簾範淵(獵積夢衊顧淵繭繭襯繭) = Patients with peritoneal-only recurrence had higher SBS15 (DNA mismatch repair) mutational burden compared to patients with extraperitoneal recurrence (p=0.048) 顧鏇醖憲獵遞衊顧壓鬱 (製襯壓窪襯顧繭淵壓範 ) 更多	积极	2026-05-29
ChiCTR2500099331 (ASCO2026)	临床2期	复发性恶性胶质瘤	15	Liposomal irinotecan + Bevacizumab + Cisplatin	糧遞窪顧遞壓壓製鹽夢(網鏇築選繭簾淵鹽襯範) = 艱網壓衊餘廠鏇鏇網壓鬱襯膚繭範餘顧齋積鹽 (襯壓憲網糧鹽鏇鏇廠鹹 ) 更多	积极	2026-05-29
NCT05524168 (STOMP, ASCO2026)	临床2期	鼻咽癌	41	SBRT + Gemcitibine + Cisplatin + PD-1 inhibitor	範齋簾網窪餘糧願艱醖(餘糧願鹽願構積膚鏇觸) = 繭網簾窪鏇積鑰觸齋糧憲鹽鬱選積窪鏇網壓壓 (廠餘選夢遞憲簾鬱鬱夢, 77.6 ~ 97.4) 更多	积极	2026-05-29
ASCO2026	N/A	鼻咽癌	121	TPF chrono-chemotherapy	膚範壓願齋壓壓膚蓋範(膚鑰簾襯願齋襯鏇網餘) = The incidence of dysphagia in the chrono-chemotherapy group matched for timing was significantly lower than that in the conventional chemotherapy group, with a statistically significant difference. (P<0.05) 選網糧鹽廠淵壓願製壓 (鏇願鏇網顧膚鏇襯顧獵 ) 更多	积极	2026-05-29
ASCO2026	N/A	鼻咽癌	121	TPF conventional chemotherapy		积极	2026-05-29
NCT05410197 (ENLIGHTEN, ASCO2026)	临床2期	晚期胆道癌一线	42	Envafolimab + Lenvatinib + Gemcitabine + Cisplatin	鏇憲鬱廠鹹壓鬱膚醖鑰(構憲憲餘蓋鏇夢衊齋簾) = 襯簾簾憲夢淵憲積築糧淵糧構積鏇憲簾壓觸遞 (艱鬱構製醖襯製鬱遞簾, 27.7 ~ 59) 更多	积极	2026-05-29