Modeling cancer using patient-derived induced pluripotent stem cells to understand development of childhood malignancies

Abstract

In vitro modeling of complex diseases is now a possibility with the use of patient-derived induced pluripotent stem (iPS) cells. Their stem cell properties, including self-renewal and their potential to virtually differentiate into any cell type, emphasize their importance as a translational tool for modeling disorders that so far have been limited by the unavailability of primary cell lines, animal models, or inaccessible human materials. Around 100 genes with germline mutations have been described to be responsible for cancer predisposition. Familial cancers are usually diagnosed earlier in life since these patients already carry the first transforming hit. Deriving iPS cells from patients suffering from familial cancers provides a valuable tool for understanding the mechanisms underlying pediatric cancer onset and progression since they require less mutation recurrence than adult cancers to develop. At the same time, some familial mutations are found in sporadic cases and are a valuable prognostic tool. Patient-derived iPS cells from germline malignancies can also create new tools in developing specific drugs with more personalized-therapy strategies.

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

“…iPSCs can be used to observe associations between genotype and responses to anticancer drugs. Their wide developmental potential makes it possible to study the effects of a specific cancer genotype or specific driver mutations [ 103 ]. iPSCs were obtained from patients with familial cancer syndromes.…”

Patient-Derived In Vitro Models for Drug Discovery in Colorectal Carcinoma

“…Expanding and maintaining tissue-derived cell lines in culture often implicates the use of exogenous immortalization methods to keep cells in culture. These cells exhibit a similar gene expression and epigenetic profile, and can be propagated in vitro, into several germ layers, providing great potential for disease modelling such as cancer [ 31 , 32 , 33 , 34 ].…”

Induced pluripotent stem cells, a giant leap for mankind therapeutic applications

“…Interestingly, primary cancer cells from different types of human cancers, such as melanoma, gastric cancer, glioblastoma and pancreatic ductal adenocarcinoma, among others, have been successfully reprogrammed into iPSC or at least into pluripotent cells, offering new possibilities to study early stages of cancer initiation and progression in vitro [38,39]. iPSC might be especially useful to model cancers emerging at young ages or with familial inherited characteristics, since these cancers have an early onset which may be promoted by the embryonic developmental process itself, which is recapitulated to a large extent during iPSC differentiation.…”