Lou Xin, Qin Yi, Xu Xiaowu, Yu Xianjun, Ji Shunrong
Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188782. doi: 10.1016/j.bbcan.2022.188782. Epub 2022 Aug 24.
During the course of pancreatic neuroendocrine tumors (NETs), they generally become more heterogeneous with individual cells exhibiting distinct molecular fingerprints. This heterogeneity manifests itself through an unequal distribution of genetically-variant, tumor cell subpopulations within disease locations (i.e., spatial heterogeneity) or changes in the genomic landscape over time (i.e., temporal heterogeneity); these characteristics complicate clinical diagnosis and treatment. Effective, feasible tumor heterogeneity detection and eradication methods are essential to overcome the clinical challenges of pancreatic NETs. This review explores the molecular fingerprints of pancreatic NETs and the spectrum of tumoral heterogeneity. We then describe the challenges of assessing heterogeneity by liquid biopsies and imaging modalities and the therapeutic challenges for pancreatic NETs. In general, navigating these challenges, refining approaches for translational research, and ultimately improving patient care are available once we have a better understanding of intratumoral spatiotemporal heterogeneity.
在胰腺神经内分泌肿瘤（NETs）的病程中，它们通常会变得更加异质性，单个细胞表现出独特的分子特征。这种异质性通过疾病部位内基因变异的肿瘤细胞亚群分布不均（即空间异质性）或随着时间推移基因组格局的变化（即时间异质性）表现出来；这些特征使临床诊断和治疗变得复杂。有效、可行的肿瘤异质性检测和根除方法对于克服胰腺NETs的临床挑战至关重要。本综述探讨了胰腺NETs的分子特征和肿瘤异质性的范围。然后，我们描述了通过液体活检和成像方式评估异质性的挑战以及胰腺NETs的治疗挑战。一般来说，一旦我们更好地理解肿瘤内时空异质性，就可以应对这些挑战、完善转化研究方法并最终改善患者护理。
