Chang David K, Grimmond Sean M, Biankin Andrew V
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland G4 0SF, United Kingdom; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW 2200, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, NSW 2170, Australia.
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD, Australia.
Curr Opin Genet Dev. 2014 Feb;24:74-81. doi: 10.1016/j.gde.2013.12.001. Epub 2014 Jan 28.
Pancreatic cancer is one of the most lethal malignancies. The overall median survival even with treatment is only 6-9 months, with almost 90% succumbing to the disease within a year of diagnosis. It is characterised by an intense desmoplastic stroma that may contribute to therapeutic resistance, and poses significant challenges for genomic sequencing studies. It is recalcitrant to almost all therapies and consequently remains the fourth leading cause of cancer death in Western societies. Genomic studies are unveiling a vast heterogeneity of mutated genes, and this diversity may explain why conventional clinical trial designs have mostly failed to demonstrate efficacy in unselected patients. Those that are available offer only marginal benefits overall, but are associated with clinically significant responses in as yet undefined subgroups. This chapter describes our current understanding of the genomics of pancreatic cancer and the potential impact of these findings on our approaches to treatment.
胰腺癌是最致命的恶性肿瘤之一。即便接受治疗,总体中位生存期也仅为6至9个月,近90%的患者在确诊后一年内死于该疾病。其特征是存在致密的促纤维增生性基质,这可能导致治疗耐药,并给基因组测序研究带来重大挑战。几乎所有疗法对其都难以奏效,因此它仍是西方社会癌症死亡的第四大主要原因。基因组研究揭示了突变基因的巨大异质性,这种多样性或许可以解释为何传统临床试验设计大多未能在未经筛选的患者中显示出疗效。现有疗法总体仅带来微小益处,但在尚未明确的亚组患者中会产生具有临床意义的反应。本章阐述了我们目前对胰腺癌基因组学的理解以及这些发现对我们治疗方法可能产生的影响。