Advancements in Preclinical Models of Pancreatic Cancer

Abstract

Pancreatic cancer remains one of the deadliest of all cancer types with a 5-year overall survival rate of just 12%. Preclinical models available for understanding the disease pathophysiology have evolved significantly in recent years. Traditionally, commercially available 2-dimensional cell lines were developed to investigate mechanisms underlying tumorigenesis, metastasis, and drug resistance. However, these cells grow as monolayer cultures that lack heterogeneity and do not effectively represent tumor biology. Developing patient-derived xenografts and genetically engineered mouse models led to increased cellular heterogeneity, molecular diversity, and tissues that histologically represent the original patient tumors. However, these models are relatively expensive and very timing consuming. More recently, the advancement of fast and inexpensive in vitro models that better mimic disease conditions in vivo are on the rise. Three-dimensional cultures like organoids and spheroids have gained popularity and are considered to recapitulate complex disease characteristics. In addition, computational genomics, transcriptomics, and metabolomic models are being developed to simulate pancreatic cancer progression and predict better treatment strategies. Herein, we review the challenges associated with pancreatic cancer research and available analytical models. We suggest that an integrated approach toward using these models may allow for developing new strategies for pancreatic cancer precision medicine.

Advancements in Circulating Tumor Cell Research: Bridging Biology and Clinical Applications

“…In a non-small cell lung cancer (NSCLC) study, the authors were able to detect different gene signatures related to therapy resistance (MET and HER3) and the initiation of metastasis (ALHD1) using CTCs [ 49 ]. The spectrum of cancer heterogeneity has long been under scrutiny as a factor allowing the tumor to adapt to different microenvironmental stressors with different subpopulations that may evolve to increase disease aggressiveness and decrease therapeutic response [ 50 ]. The study of CTCs, therefore, allows researchers to understand and monitor tumor heterogeneity, providing crucial information for devising effective and personalized treatment strategies.…”