In this study, a novel series of 53 PDOs wasĮstablished from human tumor tissues, including those from the Utilizing HTS and PDOs for the evaluation of anticancer agents have Understanding of cancer biology and for the evaluation of drugĮfficacy in vitro, prior to employing PDXs. These PDOs are promising models to facilitate a better Which have been used to evaluate anticancer agents ( 20– 23). colon, lung and endometrium) have been established, Preparation and culture as such, CTOSs from various types of tumor Principle of retaining cell-cell contact throughout cancer cell In addition,Ī cancer tissue-originated spheroid (CTOS) method based on the High-throughput screening (HTS) using these systems. Lung, kidney, ovarian, pancreatic, prostate, stomach and uterineĬancers, among others, in addition to the development of In particular,ĥ6 PDOs that were established from bladder, breast, brain, colon, ( 12– 14), pancreatic ( 15), prostate ( 16), endometrial ( 17), and liver ( 18) tumors, among others. Human tumor organoids has been recently reported for colon Or spheroid models that accurately recapitulate tissue architectureĪnd function, have been developed recently. Vitro systems, including patient-derived tumor organoid (PDO) Therefore, since cost-effective techniques are required, in Nature and high associated cost ( 6– 10). In corresponding xenografts however, the evaluation of anticancerĪgents using these models is difficult due to their low-throughput Through direct comparisons between responses in patients and those Increasing evidence suggests that PDXs closely recapitulate humanĬancer biology and may be used to predict patient drug responses The diversity of human cancer biology ( 6– 11). (PDXs) are used as preclinical cancer models that better replicate In fact, ~85% of preclinical agents entering oncologyĬlinical trials fail to demonstrate sufficient safety or efficacyĬurrently, patient-derived tumor xenograft models Identical to the results of evaluations performed with cancer cell Therefore, the clinical effects of anticancer agents are not InĪddition, almost all cell lines are cultured under monolayerĬonditions or used as xenografts in mice, which is not physically Their genome sequence, gene expression profile and morphology. Reflect the characteristics of the source tumor tissues, as theyĪre frequently passaged for long periods of time, which may alter Widely used for studies on cancer biology or as preclinical models Historically, human cancer cell lines have been Therefore, assay systems using F‑PDOs may be utilized to evaluate anticancer agents using conditions that better reflect clinical conditions, compared with conventional methods using cancer cell lines, and to discover markers that identify the pharmacological effects of anticancer agents. REME9 and 11, which were established from tumors that originated in patients who did not respond to paclitaxel and carboplatin (the standard chemotherapy for endometrial cancer), exhibited high resistance (half-maximal inhibitory concentration >10 µM) to the two agents. REME9 and 11 exhibited distinct responses and increased resistance to the drugs, as compared with conventional cancer cell lines (AN3 CA and RL95-2). A suitable high-throughput assay system, with 96- or 384‑well plates, was designed for each F‑PDO, and the efficacy of the anticancer agents was subsequently evaluated. These were used for cell growth inhibition experiments using anticancer agents. The present study represents a detailed analysis of three F‑PDOs (termed REME9, 11 and 16) established from endometrial cancer tissues. In addition, the in vivo tumorigenesis of certain F‑PDOs was confirmed using a xenograft model. At present, 53 PDOs have been established by the Fukushima Translational Research Project, and were designated as Fukushima PDOs (F‑PDOs). Comparative histological and comprehensive gene expression analyses proved that the characteristics of PDOs were similar to those of their source tumors, even following long-term expansion in culture. PDOs were able to be cultured for >6 months, and formed cell clusters with similar morphologies to their source tumors. To overcome this limitation, patient-derived tumor organoids (PDOs) were established from human lung, ovarian and uterine tumor tissues, among others, to accurately and efficiently recapitulate the tissue architecture and function. Patient-derived tumor xenograft models represent a promising preclinical cancer model that better replicates disease, compared with traditional cell culture however, their use is low-throughput and costly.
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