Smith Olivia M, Lintern Nicole, Tian Jiahao, Mesquita Bárbara M, Oliveira Sabrina, Vymetalkova Veronika, Prakash Jai, Smith Andrew M, Jayne David G, Heger Michal, Khaled Yazan S
Leeds Institute of Medical Research, St. James's University Teaching Hospital, Leeds LS9 7TF, UK.
Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, College of Medicine, Jiaxing University, Jiaxing 314001, China.
Int J Mol Sci. 2025 Jul 2;26(13):6388. doi: 10.3390/ijms26136388.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is associated with poor prognosis. Despite years of research and improvements in chemotherapy regimens, the 5-year survival rate of PDAC remains dismal. Therapies for PDAC often face resistance owing in large part to an extensive desmoplastic stromal matrix. Modelling PDAC ex vivo to investigate novel therapeutics is challenging due to the complex tumour microenvironment and its heterogeneity in native tumours. Development of novel therapies is needed to improve PDAC survival rates, for which disease models that recapitulate the tumour biology are expected to bear utility. This review focuses on the existing preclinical models for human PDAC and discusses advancements in tissue remodelling to guide translational PDAC research. Further emphasis is placed on photodynamic therapy (PDT) due to the ability of this treatment modality to not only directly kill cancer cells by minimally invasive means, but also to perturb the tumour microenvironment and elicit a post-therapeutic anti-tumour immune response. Accordingly, more complex preclinical models that feature multiple biologically relevant PDAC components are needed to develop translatable PDT regimens in a preclinical setting.
胰腺导管腺癌(PDAC)是最常见的胰腺癌类型,预后较差。尽管经过多年研究以及化疗方案有所改进,但PDAC的5年生存率仍然很低。PDAC的治疗常常面临耐药性,这在很大程度上归因于广泛的促纤维增生性基质。由于天然肿瘤中复杂的肿瘤微环境及其异质性,在体外模拟PDAC以研究新型疗法具有挑战性。需要开发新的疗法来提高PDAC的生存率,为此,能够重现肿瘤生物学特性的疾病模型有望发挥作用。本综述重点关注现有的人类PDAC临床前模型,并讨论组织重塑方面的进展,以指导转化性PDAC研究。由于光动力疗法(PDT)不仅能够通过微创手段直接杀死癌细胞,还能扰乱肿瘤微环境并引发治疗后的抗肿瘤免疫反应,因此对其给予了更多关注。因此,需要更复杂的临床前模型,这些模型具有多个生物学相关的PDAC成分,以便在临床前环境中开发可转化的PDT方案。