Applications of patient-derived tumor xenograft models and tumor organoids DOI Creative Commons
Go J. Yoshida

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Jan. 7, 2020

Abstract Patient-derived tumor xenografts (PDXs), in which fragments surgically dissected from cancer patients are directly transplanted into immunodeficient mice, have emerged as a useful model for translational research aimed at facilitating precision medicine. PDX susceptibility to anti-cancer drugs is closely correlated with clinical data patients, whom models been derived. Accumulating evidence suggests that highly effective predicting the efficacy of both conventional and novel therapeutics. This also allows “co-clinical trials,” pre-clinical investigations vivo trials could be performed parallel or sequentially assess drug PDXs. However, heterogeneity present original samples constitutes an obstacle application models. Moreover, human stromal cells originally tumors gradually replaced by host xenograft grows. replacement murine stroma preclude analysis tumor-stroma interactions, some mouse cytokines might not affect carcinoma The review highlights biological significance three-dimensional patient-derived organoid cultures several kinds solid tumors, such those colon, pancreas, brain, breast, lung, skin, ovary.

Language: Английский

Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients DOI Open Access
Salo Ooft, Fleur Weeber, Krijn K. Dijkstra

et al.

Science Translational Medicine, Journal Year: 2019, Volume and Issue: 11(513)

Published: Oct. 9, 2019

There is a clear and unmet clinical need for biomarkers to predict responsiveness chemotherapy cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions identify nonresponders standard-of-care colorectal cancer (CRC). In prospective study, we show the feasibility of generating testing PDOs evaluation sensitivity chemotherapy. Our PDO predicted response biopsied lesion more than 80% patients treated with irinotecan-based therapies without misclassifying who would have benefited treatment. This correlation was specific chemotherapy, however, failed outcome treatment 5-fluorouracil plus oxaliplatin. data suggest that could be used prevent undergoing ineffective

Language: Английский

Citations

603
Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening DOI Creative Commons
Minsuh Kim,

Hyemin Mun,

Chang Ohk Sung

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 5, 2019

Abstract Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung organoids normal bronchial established from patient tissues comprising five histological subtypes of non-neoplastic mucosa as in vitro models representing individual patient. The recapitulate the tissue architecture primary tumours maintain genomic alterations original during long-term expansion vitro. cellular components mucosa. respond to drugs based on their alterations: BRCA2-mutant organoid olaparib, an EGFR-mutant erlotinib, EGFR-mutant/MET-amplified crizotinib. Considering short length time establishment drug testing, our newly developed model may prove useful predicting patient-specific responses through trials.

Language: Английский

Citations

595
A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening DOI Creative Commons
Helen H.N. Yan,

Hoi Cheong Siu,

Simon Law

et al.

Cell stem cell, Journal Year: 2018, Volume and Issue: 23(6), P. 882 - 897.e11

Published: Oct. 18, 2018

Language: Английский

Citations

574
Targeted therapy for hepatocellular carcinoma DOI Creative Commons
Ao Huang, Xin–Rong Yang, Wen Yuan Chung

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Aug. 11, 2020

Abstract The last 3 years have seen the emergence of promising targeted therapies for treatment hepatocellular carcinoma (HCC). Sorafenib has been mainstay a decade and newer modalities were ineffective did not confer any increased therapeutic benefit until introduction lenvatinib which was approved based on its non-inferiority to sorafenib. subsequent success regorafenib in HCC patients who progress sorafenib heralded new era second-line quickly followed by ramucirumab, cabozantinib, most influential, immune checkpoint inhibitors (ICIs). Over same period combination therapies, including anti-angiogenesis agents with ICIs, dual ICIs conjunction surgery or other loco-regional extensively investigated shown promise provided basis exciting clinical trials. Work continues develop additional novel could potentially augment presently available options understand underlying mechanisms responsible drug resistance, goal improving survival HCC.

Language: Английский

Citations

556
Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer DOI Creative Commons
Ye Yao, Xiaoya Xu, Lifeng Yang

et al.

Cell stem cell, Journal Year: 2019, Volume and Issue: 26(1), P. 17 - 26.e6

Published: Nov. 21, 2019

Language: Английский

Citations

555
Establishment of patient-derived cancer organoids for drug-screening applications DOI
Else Driehuis, Kai Kretzschmar, Hans Clevers

et al.

Nature Protocols, Journal Year: 2020, Volume and Issue: 15(10), P. 3380 - 3409

Published: Sept. 14, 2020

Language: Английский

Citations

468
Organoids DOI Creative Commons
Zixuan Zhao, Xinyi Chen, Anna M. Dowbaj

et al.

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Dec. 1, 2022

Organoids have attracted increasing attention because they are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function corresponding vivo tissue. They can be dissected interrogated for fundamental mechanistic studies on development, regeneration, repair human tissues. also used diagnostics, disease modeling, drug discovery, personalized medicine. derived from either pluripotent or tissue-resident stem (embryonic adult) progenitor differentiated cells healthy diseased tissues, such as tumors. To date, numerous organoid engineering strategies support culture growth, proliferation, differentiation maturation been reported. This Primer serves to highlight rationale underlying selection development these materials methods control cellular/tissue niche; therefore, engineered organoid. We discuss key considerations generating robust organoids, those related cell isolation seeding, matrix soluble factor selection, physical cues integration. The general standards data quality, reproducibility deposition within community is outlined. Lastly, we conclude by elaborating limitations organoids different applications, priorities coming years.

Language: Английский

Citations

463
A rectal cancer organoid platform to study individual responses to chemoradiation DOI
Karuna Ganesh, Chao Wu,

Kevin P. O’Rourke

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(10), P. 1607 - 1614

Published: Oct. 1, 2019

Language: Английский

Citations

436
Human Organoids: Tools for Understanding Biology and Treating Diseases DOI

Frans Schutgens,

Hans Clevers

Annual Review of Pathology Mechanisms of Disease, Journal Year: 2019, Volume and Issue: 15(1), P. 211 - 234

Published: Sept. 25, 2019

Organoids are in vitro-cultured three-dimensional structures that recapitulate key aspects of vivo organs. They can be established from pluripotent stem cells and adult cells, the latter being subject this review. derived exploit tissue regeneration process is driven by these they directly healthy or diseased epithelium many amenable to any experimental approach has been developed for cell lines. Applications biology involve modeling physiology disease, including malignant, hereditary, infectious diseases. Biobanks patient-derived tumor organoids used drug development research, hold promise developing personalized regenerative medicine. In review, we discuss applications cell-derived laboratory clinic.

Language: Английский

Citations

406
Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer DOI Creative Commons
Émilie Picard, Chris P. Verschoor,

W Kitonyi Grace

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: March 6, 2020

Colorectal cancer (CRC) is highly heterogeneous at the genetic and molecular level, which has major repercussions on efficacy of immunotherapy. A small subset CRCs exhibit microsatellite instability (MSI), a indicator defective DNA mismatch repair (MMR), but majority are microsatellite-stable (MSS). The high tumor mutational burden (TMB) neoantigen load in MSI tumors favors infiltration immune effector cells, antitumor responses within these strong relative to their MSS counterparts. emerged as predictive marker for checkpoint blockade over last few years nivolumab or pembrolizumab targeting PD-1 been approved patients with refractory metastatic CRC. However, some show polymerase epsilon (POLE) mutations that also confer very TMB may be heavily infiltrated by cells making them amenable respond inhibitors (ICI). In this review we discuss role different landscapes CRC relationships defined subtypes. We potential reasons why met limited success patients, despite finding cell primary non-metastatic prognostic factor relapse survival. then consider ways develop mechanisms resist ICI. Finally, address latest advances vaccination how personalized vaccine strategy might overcome resistance whom not treatment option.

Language: Английский

Citations

403