Pancreatic cancer (PDAC) is one of the deadliest types of human cancers, owing to late stage at presentation and pervasive therapeutic resistance. The extensive tumour heterogeneity, as well as substantial crosstalk between the neoplastic epithelium and components within the microenvironment are the defining features of PDAC biology that dictate the dismal natural history. Recent advances in genomic and molecular profiling have informed on the genetic makeup and evolutionary patterns of tumour progression, leading to treatment breakthroughs in minor subsets of patients with specific tumour mutational profiles. The nature and function of tumour heterogeneity, including stromal heterogeneity, in PDAC development and therapeutic resistance, are increasingly being elucidated. Deep insight has been gained regarding the metabolic and immunological deregulation, which further sheds light on the complex biology and the observed treatment recalcitrance. Here we will summarize these recent achievements and offer our perspective on the path forward.

胰腺癌 (PDAC) 是最致命的人类癌症之一，因为其发病时已处于晚期且普遍存在治疗耐药性。广泛的肿瘤异质性以及肿瘤上皮与微环境内成分之间的大量串扰是 PDAC 生物学的决定性特征，决定了令人沮丧的自然史。基因组和分子谱分析的最新进展揭示了肿瘤进展的基因组成和进化模式，从而为具有特定肿瘤突变谱的少数患者带来了治疗突破。肿瘤异质性（包括基质异质性）在 PDAC 发展和治疗耐药中的性质和功能日益得到阐明。人们对代谢和免疫失调有了深入的了解，这进一步揭示了复杂的生物学和观察到的治疗顽抗。在这里，我们将总结这些最近的成就，并提出我们对未来道路的看法。