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用于乳腺癌的抗体药物偶联物:一项文献计量学研究与临床试验分析

Antibody-drug conjugates for breast cancer: a bibliometric study and clinical trial analysis.

作者信息

Xing Mengjie, Li Zhiyi, Cui Yuwan, He Minghua, Xing Yang, Yang Lei, Liu Ziling, Luo Linzhi, Wang Hong, Guo Rui

机构信息

Department of Clinical Laboratory, First Bethune Hospital of Jilin University, Changchun, China.

First Bethune Hospital of Jilin University, Changchun, China.

出版信息

Discov Oncol. 2024 Aug 2;15(1):329. doi: 10.1007/s12672-024-01192-w.


DOI:10.1007/s12672-024-01192-w
PMID:39093344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297011/
Abstract

BACKGROUND: Breast cancer (BC) remains the most commonly malignancy among women worldwide. Although early-stage BC typically presents with curative possibilities, advanced-stage disease, especially with metastasis, is significantly limited in terms of effective therapeutic interventions, thereby establishing it as the second leading cause of cancer-related deaths in women. Antibody-Drug Conjugates (ADCs) establish a groundbreaking class of anti-neoplastic agents characterized by high specificity and targeting precision. These agents have been significant in reshaping the therapeutic approach to breast cancer, especially those subtypes with overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2). Comprising monoclonal antibodies, cytotoxic payloads, and conjugative linkers, ADCs function by specifically targeting antigens on cancer cells, thereby facilitating the intracellular delivery of the toxic payload. The present investigation endeavors to synthesize existing primary research outcomes through rigorous bibliometric and data analytical approaches, thereby elucidating the current research landscape, delineating research foci, and identifying potential avenues for future innovation. METHODS: For bibliometric analysis, a comprehensive data set comprising 2181 entries related to ADCs in breast cancer was retrieved from the Web of Science Core Collection (WoSCC) spanning the years 1999 to 2023. This data was further filtered from the Science Citation Index Expanded (SCI-Expanded). Analysis software tools such as CiteSpace and VOSviewer were employed for multifaceted analyses such as trends of publications, contributions of countries, and burst analytics. In the dimension of clinical trials, we interrogated databases including ClinicalTrials.gov ( https://www. CLINICALTRIALS: gov ) and the WHO International Clinical Trials Registry Platform (ICTRP) ( https://trialsearch.who.int ). A total of 239 clinical trials were initially sourced, among which, 175 were from ClinicalTrials.gov and 64 from ICTRP. After repetitive and correlation-based screening, 119 trials specifically addressing ADC therapeutic strategies in breast cancer were included. Analytical algorithms were executed using Microsoft-based software to evaluate treatment paradigms, emergent research themes, and progress. RESULTS: Our investigations signify a growing trend of research on ADCs, with consistent advancements in scientific achievements. The analysis revealed that variables such as economic stratification of nations, healthcare investment paradigms, and disease incidence rates serve as significant determinants in shaping research output. Geographically, the United States emerged as the predominant contributor to the research corpus (36.56%), closely followed by China (21.33%). The underpinning of research accomplishments was found to be significantly bolstered by advancements in molecular biology, immunology, and genetic research. Moreover, the advent of nuclear magnetic resonance diagnostic modalities has contributed saliently to the diagnostic and therapeutic management of breast cancer. CONCLUSION: Our study provides a comprehensive overview of the ADC research landscape through rigorous bibliometric and clinical trial evaluations. At present, the ADC arena has witnessed the successful development and FDA approval of 14 distinct agents, substantially improving the clinical outcomes for a broad spectrum of oncological patients. Future research imperatives may include the exploration of ADCs targeting mutated oncoproteins, dual-specificity ADCs, combination payload strategies, peptide-drug conjugates (PDCs), and non-internalizing ADC modalities. With sustained academic and clinical focus, the ADC domain is poised for transformative advancements in targeted therapeutics across a variety of malignancies.

摘要

背景:乳腺癌(BC)仍是全球女性中最常见的恶性肿瘤。尽管早期乳腺癌通常具有治愈的可能性,但晚期疾病,尤其是发生转移的情况,在有效治疗干预方面受到显著限制,因此它成为女性癌症相关死亡的第二大主要原因。抗体 - 药物偶联物(ADCs)是一类具有开创性的抗肿瘤药物,其特点是高特异性和靶向精准度。这些药物在重塑乳腺癌的治疗方法方面具有重要意义,尤其是对于人类表皮生长因子受体2(HER2)过表达的那些亚型。ADCs由单克隆抗体、细胞毒性有效载荷和连接子组成,通过特异性靶向癌细胞上的抗原发挥作用,从而促进有毒有效载荷的细胞内递送。本研究致力于通过严格的文献计量学和数据分析方法综合现有的初步研究成果,从而阐明当前的研究格局,勾勒研究重点,并确定未来创新的潜在途径。 方法:对于文献计量分析,从1999年至2023年的科学引文索引扩展版(SCI - Expanded)中检索了Web of Science核心合集(WoSCC)中包含的2181条与乳腺癌中ADCs相关的条目组成的综合数据集。使用CiteSpace和VOSviewer等分析软件工具进行多方面分析,如出版物趋势、国家贡献和爆发分析。在临床试验方面,我们查询了包括ClinicalTrials.gov(https://www.CLINICALTRIALS.gov)和世界卫生组织国际临床试验注册平台(ICTRP)(https://trialsearch.who.int)在内的数据库。最初共获取了239项临床试验,其中175项来自ClinicalTrials.gov,64项来自ICTRP。经过基于重复和相关性的筛选,纳入了119项专门针对乳腺癌中ADC治疗策略的试验。使用基于微软的软件执行分析算法,以评估治疗模式、新兴研究主题和进展。 结果:我们的研究表明,关于ADCs的研究呈增长趋势,科学成就不断进步。分析显示,国家经济分层、医疗保健投资模式和疾病发病率等变量是影响研究产出的重要决定因素。在地理上,美国是研究文献的主要贡献者(36.56%),紧随其后的是中国(21.33%)。分子生物学、免疫学和基因研究的进展显著推动了研究成果的基础。此外,核磁共振诊断方式的出现对乳腺癌的诊断和治疗管理做出了重要贡献。 结论:我们的研究通过严格的文献计量学和临床试验评估,全面概述了ADC研究格局。目前,ADC领域见证了14种不同药物的成功开发和美国食品药品监督管理局(FDA)的批准,显著改善了广泛肿瘤患者的临床结局。未来的研究重点可能包括探索靶向突变癌蛋白的ADCs、双特异性ADCs、联合有效载荷策略、肽 - 药物偶联物(PDCs)和非内化ADC模式。随着学术和临床的持续关注,ADC领域有望在各种恶性肿瘤的靶向治疗方面实现变革性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/4e276542ba89/12672_2024_1192_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/34760d052f28/12672_2024_1192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/51ce0a033e0f/12672_2024_1192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/de6238c8fea1/12672_2024_1192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/0f7ca70e800e/12672_2024_1192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/4e276542ba89/12672_2024_1192_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/2ccc6ed0b2e7/12672_2024_1192_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/fec871c6ffc8/12672_2024_1192_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/97de8998f6c8/12672_2024_1192_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/34760d052f28/12672_2024_1192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/51ce0a033e0f/12672_2024_1192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/de6238c8fea1/12672_2024_1192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/0f7ca70e800e/12672_2024_1192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/badd/11297011/4e276542ba89/12672_2024_1192_Fig8_HTML.jpg

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[1]
The "lows": Update on ER-low and HER2-low breast cancer.

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Antibody-Drug Conjugates for Breast Cancer Treatment: Emerging Agents, Targets and Future Directions.

Int J Mol Sci. 2023-7-25

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Future Oncol. 2023-11

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[4]
TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer.

Future Oncol. 2024-3

[5]
Optimizing the safety of antibody-drug conjugates for patients with solid tumours.

Nat Rev Clin Oncol. 2023-8

[6]
HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic -mutated NSCLC.

Future Oncol. 2023-6

[7]
B7-H3 immunoregulatory roles in cancer.

Biomed Pharmacother. 2023-7

[8]
Research trends and prospects on brain metastasis from breast cancer: A bibliometric analysis.

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