摘要
Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide.In the setting of resectable disease,there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival.Disappointingly,only 15%-30%of patients obtain a histopathological response to neoadjuvant therapy,often at the expense of significant toxicity.There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes.In this review,we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting.We place these issues in the wider context of recommendations for biomarker development and reporting.The majority of studies focus on messenger RNA(mRNA)and microRNA(miRNA)biomarkers.These studies report a range of different genes involved in a wide variety of pathways and biological processes,and this is explained to a large extent by the different platforms and analysis methods used.Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker.Multiple molecular subtypes of oesophageal cancer have been proposed,although little is known about how these relate to clinical outcomes.We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.
食管癌是一种预后较差的致死性疾病,其死亡率排在恶性肿瘤第六位。证据表明,对于可手术切除的食管肿瘤,新辅助化疗和放化疗可以改善生存。遗憾的是,只有15%-30%的患者对新辅助治疗有反应,且常出现毒性反应。目前临床上尚无有效的预测标志物,无法对患者进行个体化治疗以显著改善疗效。本文对用于预测食管癌新辅助治疗反应的生物标志物的当前进展进行综述,并对生物标志物的研发所面临的挑战展开讨论。我们将这些问题与对生物标志物开发和报道的建议相联系进行探讨。目前大多数生物标志物研究集中在mRNA和miRNA,这些研究报道了涉及多条信号通路和生物学过程的诸多不同基因,很大程度上是由于不同的研究平台和不同的分析方法造成的。而且许多研究也因过于薄弱,不足以鉴定出可能的生物标志物。尽管多种食管癌分子亚型被提出,但其与临床结局的关系我们知之甚少。我们预测,未来几年随着基因组数据与临床试验协作研究成果的不断积累,对食管癌患者进行分层从而实现个体化治疗将成为可能。我们建议,未来生物标志物的研发应融入到精心设计的回顾性和前瞻性临床研究中。
基金
supported by the Wellcome Trust and the Health Research Board[Grant Number 203930/B/16/Z]
the Health Service Executive National Doctors Training and Planning
the Health and Social Care Research and Development Division,Northern Ireland.
