Martinez-Ruiz Laura, López-Rodríguez Alba, Florido Javier, Rodríguez-Santana Cesar, Rodríguez Ferrer José M, Acuña-Castroviejo Darío, Escames Germaine
Institute of Biotechnology, Biomedical Research Center, Health Sciences Technology Park, University of Granada, Granada, Spain; Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Investigación Biosanitaria (Ibs), Granada, San Cecilio University Hospital, Granada, Spain; Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Granada, Spain.
Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain; Department of Biochemistry and Molecular Biology I, Faculty of Science, University of Granada, Granada, Spain.
Biomed Pharmacother. 2023 Nov;167:115581. doi: 10.1016/j.biopha.2023.115581. Epub 2023 Sep 23.
The development of new anticancer therapies tends to be very slow. Although their impact on potential candidates is confirmed in preclinical studies, ∼95 % of these new therapies are not approved when tested in clinical trials. One of the main reasons for this is the lack of accurate preclinical models. In this context, there are different patient-derived models, which have emerged as a powerful oncological tool: patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived cells (PDCs). Although all these models are widely applied, PDXs, which are created by engraftment of patient tumor tissues into mice, is considered more reliable. In fundamental research, the PDX model is used to evaluate drug-sensitive markers and, in clinical practice, to select a personalized therapeutic strategy. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. However, the literature regarding the oncostatic effect of melatonin in patient-derived tumor models is scant. This review aims to describe the important role of patient-derived models in the development of anticancer treatments, focusing, in particular, on PDX models, as well as their use in cancer research. This review also summarizes the existing literature on the anti-tumoral effect of melatonin in patient-derived models in order to propose future anti-neoplastic clinical applications.
新型抗癌疗法的研发往往非常缓慢。尽管在临床前研究中已证实它们对潜在候选对象有影响,但在临床试验中进行测试时,约95%的这些新疗法未获批准。造成这种情况的主要原因之一是缺乏准确的临床前模型。在这种背景下,出现了不同的患者来源模型,它们已成为一种强大的肿瘤学工具:患者来源异种移植瘤(PDX)、患者来源类器官(PDO)和患者来源细胞(PDC)。尽管所有这些模型都得到了广泛应用,但通过将患者肿瘤组织植入小鼠体内创建的PDX被认为更可靠。在基础研究中,PDX模型用于评估药物敏感标志物,在临床实践中,则用于选择个性化治疗策略。褪黑素因其抑癌作用和缺乏不良反应,在创新癌症治疗的研发中尤为重要。然而,关于褪黑素在患者来源肿瘤模型中的抑癌作用的文献却很少。本综述旨在描述患者来源模型在抗癌治疗研发中的重要作用,尤其侧重于PDX模型,以及它们在癌症研究中的应用。本综述还总结了现有关于褪黑素在患者来源模型中的抗肿瘤作用的文献,以便提出未来的抗肿瘤临床应用。