Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening

Kim, Minsuh; Mun, Hyemin; Sung, Chang Oak; Cho, Eun Jeong; Jeon, Hye-Joon; Chun, Sung-Min; Jung, Da-Jung; Shin, Tae Hoon; Jeong, Gi Seok; Kim, Dong Kwan; Choi, Eun Kyung; Jeong, Seong‐Yun; Taylor, Alison M.; Jain, Sejal; Meyerson, Matthew; Jang, Se Jin

doi:10.1038/s41467-019-11867-6

Cited by 527 publications

(539 citation statements)

References 67 publications

(100 reference statements)

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“…One case of third-and fourth-line chemotherapy also exhibited lack of sensitivity to docetaxel. Our results highlight the applicability of patientderived organoid drug screens to predict clinical outcome [20] and their correlation with genomic and transcriptomic features of the primary tumor, as shown in recent studies for lung [56], gastrointestinal cancer [20], hepatocellular carcinoma [57] and ovarian cancer [58]. The panel of drugs can be adapted depending on the individual patient profile e.g.…”

Section: Ar-blocker Enzalutamide Was Effective Only In the Androgen-dsupporting

confidence: 61%

Patient-derived xenografts and organoids model therapy response in prostate cancer

Karkampouna

Manna

Filippo

et al. 2020

Preprint

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Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe a novel androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa).RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor. PNPCa harbours BRCA2 and CHD1 somatic mutations, shows an SPOP/FOXA1-like transcriptomic signature and microsatellite instability, which occurs in 3% of advanced PCa and has never been modelled in vivo. Comparison of the treatment-naïve PNPCa with additional metastatic PDXs (BM18, LAPC9), in a medium-throughput organoid screen of FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX-and patient-derived organoids from advanced cases with acquired resistance to standard-of-care compounds.This proof-of-principle study may provide a preclinical tool to screen drug responses to standard-of-care and newly identified, repurposed compounds. Conflict of interest and Disclosure Statement:The authors declare no conflict of interest.

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Section: Ar-blocker Enzalutamide Was Effective Only In the Androgen-dsupporting

confidence: 61%

Patient-derived xenografts and organoids model therapy response in prostate cancer

Karkampouna

Manna

Filippo

et al. 2020

Preprint

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“…This novel protocol is fast and reproducible and provides enough material for RNA and exome sequencing, as well as drug sensitivity tests. It is thus suitable for genotype-drug association studies and opens new avenues to personalized medicine approaches, along the line of current advances in other cancer fields in which organoid biobanks have already been established or are currently being generated (Boj et al, 2015;Van De Wetering et al, 2015;Sachs et al, 2018;Yan et al, 2018;Kim et al, 2019).…”

Section: Tumorspheres and Glioblastoma Organoids From Primary Tissuementioning

confidence: 99%

Organoid Models of Glioblastoma to Study Brain Tumor Stem Cells

Azzarelli

2020

Front. Cell Dev. Biol.

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Glioblastoma represents an aggressive form of brain cancer characterized by poor prognosis and a 5-year survival rate of only 3-7%. Despite remarkable advances in brain tumor research in the past decades, very little has changed for patients, due in part to the recurrent nature of the disease and to the lack of suitable models to perform genotype-phenotype association studies and personalized drug screening. In vitro culture of cancer cells derived from patient biopsies has been fundamental in understanding tumor biology and for testing the effect of various drugs. These cultures emphasize the role of in vitro cancer stem cells (CSCs), which fuel tumor growth and are thought to be the cause of relapse after treatment. However, it has become clear over the years that a 2D monolayer culture of these CSCs has certain disadvantages, including the lack of heterogeneous cell-cell and cell-environment interactions, which can now be partially overcome by the introduction of 3D organoid cultures. This is a novel and expanding field of research and in this review, I describe the emerging 3D models of glioblastoma. I also discuss their potential to advance our knowledge of tumor biology and CSC heterogeneity, while debating their current limitations.

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“…Also, organoids received by cultivation small tissue fragments and explants on matrixes or from cultured or sorted cells assembled to organoids in vitro (Hu et al, 2018). Organoids from primary lung cancer tissues demonstrated the high reproduction levels of histological and genetic characteristics of in situ tissue and their high ability for using them in patient-specific drug trials (Kim et al, 2019). Organoid manner was used for modeling PDAC from patient derived xenografts (PDX) tumors (Nelson et al, 2020) and organoids derived from patient prostate cancer bone metastasis (Lee et al, 2020).…”

Section: Three-dimensional Culturesmentioning

confidence: 99%

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening

Kitaeva

Rutland

Rizvanov

et al. 2020

Front. Bioeng. Biotechnol.

116

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The development of new high-tech systems for screening anticancer drugs is one of the main problems of preclinical screening. Poor correlation between preclinical in vitro and in vivo data with clinical trials remains a major concern. The choice of the correct tumor model at the stage of in vitro testing provides reduction in both financial and time costs during later stages due to the timely screening of ineffective agents. In view of the growing incidence of oncology, increasing the pace of the creation, development and testing of new antitumor agents, the improvement and expansion of new high-tech systems for preclinical in vitro screening is becoming very important. The pharmaceutical industry presently relies on several widely used in vitro models, including two-dimensional models, three-dimensional models, microfluidic systems, Boyden's chamber and models created using 3D bioprinting. This review outlines and describes these tumor models including their use in research, in addition to their characteristics. This review therefore gives an insight into in vitro based testing which is of interest to researchers and clinicians from differing fields including pharmacy, preclinical studies and cell biology.

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Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening

Cited by 527 publications

References 67 publications

Patient-derived xenografts and organoids model therapy response in prostate cancer

Patient-derived xenografts and organoids model therapy response in prostate cancer

Organoid Models of Glioblastoma to Study Brain Tumor Stem Cells

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening

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