Modeling Cancer with Pluripotent Stem Cells

Abstract

The elucidation of cancer pathogenesis has been hindered by limited access to patient samples, tumor heterogeneity and the lack of reliable model organisms. Characterized by their ability to self-renew indefinitely and differentiate into all cell lineages of an organism, pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide a powerful and unlimited source to generate differentiated cells that can be used to study disease biology, facilitate drug discovery and development, and provide key insights for developing personalized therapies. This article reviews the recent developments and technologies converting PSCs into clinically relevant model systems for cancer research.

Keywords: Cancer Disease Modeling; Differentiation; Genome Editing; Pluripotent Stem Cells.

Figure 1. Application of Pluripotent Stem Cells to Study Cancer-Associated Genetic Alterations

(A) PSCs are characterized by their capability to differentiate into all derivative cell types of the three germ layers. PSCs can form blood, kidney, bone and cartilage cells via the mesoderm; ovary, breast, prostate, thyroid, liver, pancreas, lung, stomach, and intestine cells via the endoderm; and brain, eye and skin cells via the ectoderm. (B) Loss of tumor suppressor genes, such as p53 mutation; or acquisition of oncogenes, such as ERBB2 amplification or ABL1 translocation, results in both hereditary and sporadic cancers in ectodermal, mesodermal, and endodermal tissues.