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. 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. PDOs were able to be cultured for >6 months, and formed cell clusters with similar morphologies to their source tumors. 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. At present, 53 PDOs have been established by the Fukushima Translational Research Project, and were designated as Fukushima PDOs (F-PDOs). In addition, the in vivo tumorigenesis of certain F-PDOs was confirmed using a xenograft model. The present study represents a detailed analysis of three F-PDOs (termed REME9, 11 and 16) established from endometrial cancer tissues. These were used for cell growth inhibition experiments using anticancer agents. 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. REME9 and 11 exhibited distinct responses and increased resistance to the drugs, as compared with conventional cancer cell lines (AN3 CA and RL95-2). 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. 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.

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These findings indicate that the RSAR001 cell line harbors EWSR1-ATF1 type 1 chimeric fusion gene, which is specific to CCS. RSAR001 cells might be useful for investigating biological behaviors and developing new treatments such as molecular-targeting antitumor drugs or immunological drugs for CCS.

A lack of practical resources in Japan has limited preclinical discovery and testing of therapies for pediatric relapsed and refractory acute lymphoblastic leukemia (ALL), which has poor outcomes. Here, we established 57 patient‐derived xenografts (PDXs) in NOD.Cg‐Prkdcscidll2rgtm1Sug/ShiJic (NOG) mice and created a biobank by preserving PDX cells including three extramedullary relapsed ALL PDXs. We demonstrated that our PDX mice and PDX cells mimicked the biological features of relapsed ALL and that PDX models reproduced treatment‐mediated clonal selection. Our PDX biobank is a useful scientific resource for capturing drug sensitivity features of pediatric patients with ALL, providing an essential tool for the development of targeted therapies.

Loss of muscle tissues in cancer cachexia has been partly attributed to the activation of autophagy; however, because the experimental animal models involved only canonical cell lines, this conclusion cannot be confirmed until it is evaluated for different pathological conditions. Hence, in the present study, we histologically examined the punctate signal for LC3, an autophagosome marker, in patient-derived xenograft (PDX) mice. When 10 PDX mice grafted with colorectal cancer tissues were examined, their body weight, muscle (gastrocnemius) weight, and area of muscle fiber were all significantly lesser than those of control mice. In addition, immunofluorescence microscopy revealed that the number of LC3-positive puncta per muscle fiber or fiber area was significantly higher in the PDX mice than in control mice. These results indicate that the autophagy-lysosomal degradation system is involved in cancer cachexia-induced muscle wasting, and that PDX mice are a useful model for pathological analyses of cachexic muscle loss.