Organoid cultures derived from patients with advanced prostate cancer

By D. Gao, I. Vela, A. Sboner, Philip J. Iaquinta, W. Karthaus, A. Gopalan, C. Dowling, Jackie N. Wajala, Eva Undvall, V. Arora and 29 more. Cell, 2014

1,414 citations recorded by the source corpus.

Summary The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D “organoid” system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression and CHD1 loss. Whole exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as of DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.

Subfields: Cancer Research, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/b63f942ae6dfd91bbed038e0f2bbbab4d2fe8784

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Citations in the corpus

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, background): “Organoids have since been applied to model various cancers, including pancreatic, prostate, liver, breast, bladder, ovarian, and gastrointestinal cancers (Boj et al., 2015; Broutier et al., 2017; Gao et al., 2014; Kopper et al., 2019; Lee et al., 2018; Sachs et al., 2018; Yan et al., 2018).”
Genetics and biology of prostate cancer (2018, background): “Prostate cancer cells undergo EMT, disseminate into the circulation as circulating tumor cells (CTCs), and overcome several physical barriers in establishing bone metastasis, traversing sinusoid walls and bonemarrow stroma and thenmigrating to the endosteal bone surface (Body et al. 2015) via sinuso”
Liquid biopsy: current technology and clinical applications (2022, methodology): “CTCs have been used to establish cell lines for prostate [24], lung [25], breast [26], and colon cancer [27].”
Modeling Development and Disease with Organoids. (2016, background): “Cancer Once culturing protocols for human aSC-based organoids were established, we have shown the feasibility of growing organoids from primary colon, prostate, and pancreatic cancers (Boj et al., 2015; Gao et al., 2014; Sato et al., 2011; van de Wetering et al., 2015).”
Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling (2016, background): “As such, there is a clear need to develop tools that can help predict the response of individual patients to drugs [82,83].”