A promising breakthrough in pancreatic cancer research: The potential of spheroids as 3D models

Pancreatic ductal adenocarcinoma (PDAC) stands as the fourth leading cause of cancer-related deaths, primarily attributable to its resistance to chemotherapy, resulting in a nearly universal fatality rate. Despite the promise exhibited by numerous drugs in preclinical studies, their subsequent failure in clinical trials underscores the inherent limitations of conventional two-dimensional cell culture models commonly employed in early drug screening endeavors. The inadequacies of two-dimensional (2D) models prompted the exploration of threemore faithfully recapitulate the native tumor microenvironment. These 3D systems have distinct advantages over 2D models in morphology, proliferation, drug response, and protein expression. Among these 3D platforms, tumor organoids and spheroids, generated through different methodologies, have emerged as next-generation models that closely mirror aspects of pancreatic tumor biology. This comprehensive review scrutinizes pancreatic cancer spheroids' techniques, tissue sources, and applications, offering a nuanced analysis of their advantages and limitations. By comparing these distinct 3D culture systems, researchers gain valuable insights to inform the selection of optimal model designs aligned with their specific experimental objectives. The utilization of these advanced models holds significant promise for enhancing the clinical relevance of both in vitro and in vivo cancer research, thereby contributing to the development of improved therapeutics against pancreatic cancer.