Abdul Rahman Rozana, Lamarca Angela, Hubner Richard A, Valle Juan W, McNamara Mairéad G
Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester M20 4BX, UK.
Department of Medical Oncology, The Christie NHS Foundation Trust/Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK.
Cancers (Basel). 2021 Jul 27;13(15):3779. doi: 10.3390/cancers13153779.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.
胰腺导管腺癌（PDAC）是最致命的癌症之一，预计到2030年将成为癌症相关死亡的第二大常见原因，总体5年生存率在7%至9%之间。尽管最近手术、化疗和放疗技术取得了进展，但PDAC患者的预后仍然很差。预后不良是多因素的，包括就诊时亚临床转移疾病的可能性、就诊时的晚期阶段、缺乏早期和可靠的诊断生物标志物，以及围绕广泛促纤维增生性PDAC肿瘤微环境的复杂生物学特性。微生物群是指在一个环境中发现的所有微生物，而微生物组是一个环境中微生物群及其基因组的集合。这些生物体存在于身体表面和粘膜层内，但在肠道中含量最为丰富。共生微生物组在健康个体中以共生状态存在，并有助于营养、代谢和免疫调节以维持正常健康。生态失调是微生物组的扰动，可导致疾病状态，包括炎症性肠病和癌症的病因，如结直肠癌和PDAC。微生物与大约10%至20%的人类癌症有关，它们可通过影响许多癌症特征来诱导致癌作用，例如促进炎症、逃避免疫破坏，并且微生物代谢产物可在癌症发生前破坏宿主基因组稳定性。自免疫疗法出现以来，癌症治疗取得了重大进展。微生物组特征与许多实体瘤的免疫治疗反应和生存相关。然而，PDAC免疫治疗的进展一直具有挑战性。因此，本综述将重点关注已发表的关于微生物组与PDAC关联的现有证据，并探讨其作为治疗靶点的潜力。
