Clark James, Fotopoulou Christina, Cunnea Paula, Krell Jonathan
Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.
West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom.
Front Oncol. 2022 Mar 25;12:837233. doi: 10.3389/fonc.2022.837233. eCollection 2022.
Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer.
上皮性卵巢癌(EOC)是一种异质性疾病,其临床表现、病理和预后存在差异。晚期EOC的典型特征是频繁复发,尽管手术和全身治疗有所改进,但其历史5年生存率仍低于30%。下一代测序技术的出现,在许多癌症类型的个性化医疗领域取得了显著进展。然而,尽管已证明晚期EOC的生存期有显著延长,但实现治愈的成功率仍然有限。因此,有必要开发新的研究平台,以应对早期诊断和治疗领域的快速发展,同时认识到与EOC相关的显著肿瘤异质性。在现有的肿瘤模型中,患者来源的类器官(PDO)和外植体肿瘤切片作为模拟包括卵巢癌在内的不同癌症类型的新型系统,已显示出特别的前景。PDO是器官特异性的三维肿瘤培养物,能够准确代表其原发肿瘤的组织学和基因组学,还可为药物测试平台提供模型,具有时间优势,并有可能作为前瞻性个性化模型来指导临床决策。此类应用可以在个体层面上使药物治疗对患者的益处最大化,同时尽量减少使用效果不佳但有毒的疗法。PDO未来可能在学术研究和药物开发中发挥更大作用,并有潜力彻底改变未来的患者治疗和临床试验途径。同样,肿瘤切片或外植体最近在提供快速、特异性的药物测试平台方面也展现了新的前景,该平台能够准确反映肿瘤反应。肿瘤外植体保留了组织结构,因此纳入了大部分肿瘤微环境,使其成为重现病情的一种有吸引力的方法,同样具有显著的时间优势和针对患者的治疗个性化优势。本综述将讨论EOC的当前治疗格局和研究模型、它们的发展以及在发现新型生物标志物或联合治疗策略以增加卵巢癌女性治疗选择方面的新进展。