School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
Metabolic Signalling Group, Curtin Health Innovation Research Institute, Curtin Medical School, Curtin University, Perth, WA 6102, Australia.
Biomolecules. 2022 Feb 17;12(2):320. doi: 10.3390/biom12020320.
Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic efficacy. The existing therapeutic approaches such as FDA-approved chemotherapeutics, gemcitabine, abraxane and folfirinox, prolong survival marginally and are accompanied by adverse effects. Several studies suggest the role of cannabinoids as anti-cancer agents. Cannabinoid receptors are known to be expressed in pancreatic cells, with a higher expression reported in pancreatic cancer patients. Therefore, pharmacological targeting of the endocannabinoid system might offer therapeutic benefits in pancreatic cancer. In addition, emerging data suggest that cannabinoids in combination with chemotherapy can increase survival in transgenic pancreatic cancer murine models. This review provides an overview of the regulation of the expanded endocannabinoid system, or endocannabinoidome, in PDAC and will explore the potential of targeting this system for novel anticancer approaches.
胰腺导管腺癌（PDAC）是胰腺最常见的恶性肿瘤，是一种侵袭性和致命性的癌症，死亡率非常高。高度异质性、无症状的早期阶段以及缺乏特异性诊断标志物，导致当肿瘤局部进展或转移时，诊断为晚期。PDAC 对大多数可用的化疗和放疗治疗具有耐药性，使手术成为最有效的治疗方法。纤维增生性肿瘤微环境有助于确定 PDAC 的病理生理学、免疫反应和治疗效果。现有的治疗方法，如 FDA 批准的化疗药物、吉西他滨、白蛋白紫杉醇和 FOLFIRINOX，只能略微延长生存时间，并伴有不良反应。几项研究表明大麻素具有抗癌作用。已知大麻素受体在胰腺细胞中表达，在胰腺癌患者中表达更高。因此，内源性大麻素系统的药理学靶向可能在胰腺癌中提供治疗益处。此外，新出现的数据表明，大麻素与化疗联合使用可以提高转基因胰腺癌细胞小鼠模型的存活率。这篇综述概述了 PDAC 中扩展的内源性大麻素系统（内源性大麻素组）的调节，并将探讨靶向该系统用于新型抗癌方法的潜力。
