Modeling cancer progression using human pluripotent stem cell-derived cells and organoids

Abstract

Conventional cancer cell lines and animal models have been mainstays of cancer research. More recently, human pluripotent stem cells (hPSCs) and hPSC-derived organoid technologies, together with genome engineering approaches, have provided a complementary platform to model cancer progression. Here, we review the application of these technologies in cancer modeling with respect to the cell-of-origin, cancer propagation, and metastasis. We further discuss the benefits and challenges accompanying the use of hPSC models for cancer research and discuss their broad applicability in drug discovery, biomarker identification, decoding molecular mechanisms, and the deconstruction of clonal and intra-tumoral heterogeneity. In summary, hPSC-derived organoids provide powerful models to recapitulate the pathogenic states in cancer and to perform drug discovery.

In vitro models for head and neck cancer: Current status and future perspective

“…In more detail, induced pluripotent stem cell–based cancer modeling can be used as follows ( 145 ): (I) genetic alterations can be engineered into normal human-induced pluripotent stem cells using transcription activator-like effector nucleases (TALENs) or CRISPR/Cas9 ( 146 ). These stem- derived cells with engineered cancer-associated mutations can be used to acquire the initial cancer molecular events to then emulate cancer progression ( 145 ). (II) Induced pluripotent stem cells can be used to reprogram patient-specific somatic cells with cancer predisposition syndromes such as Li–Fraumeni syndrome ( 147 ).…”

“…(II) Induced pluripotent stem cells can be used to reprogram patient-specific somatic cells with cancer predisposition syndromes such as Li–Fraumeni syndrome ( 147 ). (III) Induced pluripotent stem cells can be engineered as cancer-specific cells by targeting tumor suppressors such as SMAD4, Rb/P16, BRCA1, CDKN1A, and CDKN2A ( 145 ). The previously mentioned stem cell strategies may help advance PDO research on H&N cancer.…”

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

“…Researchers have found that 3D models are particularly successful in modeling the lineage progression, cellular heterogeneity and invasive potential of these devastating cancers (see Luo and Li, 2021 for a recent review). 3D modeling approaches for glioblastoma are ever evolving and have included organoids generated from primary patient samples or hPSC derivatives, and more recently bioprinted constructs that aim to more faithfully recapitulate multiple elements of the tumor tissue microenvironment (Gimple et al, 2019 ; Zhang et al, 2020 ; Stanković et al, 2021 ). There are two main approaches to 3D cancer modeling: creating a “tumorsphere” consisting of cancer cells to model growth, signaling and drug response (Lenin et al, 2021 ; Pinto et al, 2021 ) or co-culture of cancer cells with “normal” organoids to study invasion and tumor formation (Choe et al, 2020 ; Azzarelli et al, 2021 ).…”

Progenitor cells derived from gene‐engineered human induced pluripotent stem cells as synthetic cancer cell alternatives for in vitro pharmacology

“…12 As such, hiPSCs derived from healthy donors present an unlimited resource of cells to serve as receiver matrixes for genetic elements encoding for cancer-relevant transformations. Such healthy donorderived tumor models -herein referred to as hiPSC-oncogene models -manifest themselves as a sustainable alternative disease modeling strategy in the current cancer research community [13][14][15][16][17][18] complementing the portfolio of lab tools alongside the use of PD systems. It is speculated that iPSC models of cancer, derived through synthetic approaches or reprogramming of tumor cells, may be beneficial to homogeneously depict a cell of origin of cancers.…”