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Cells
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Current Applications of Patient-Derived Cancer Model
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Current Applications of Patient-Derived Cancer Model

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (18 April 2022) | Viewed by 14047

Special Issue Editors

Dr. Tadashi Kondo

E-Mail Website
Guest Editor
Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: rare cancer research; sarcoma; biobank; precision medicine; biomarker development; target discovery; patient-derived cancer model; proteogenomics; proteomics; bioinformatics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Noriko Gotoh

E-Mail Website
Guest Editor
Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
Interests: breast cancer; cancer stem-like cells; tumor microenvironment; tumor organoids; patient-derived cancer model
Dr. Yoshitaka Hippo

E-Mail Website
Guest Editor
Division of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, 666-2, Nitona-cho, Chuo-ku, Chiba-city, Chiba 260-8717, Japan
Interests: multi-step carcinogenesis; animal models; genetic engineering; cellular transformation; organoids; preclinical models; patient-derived cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Cells collects original research and review articles that address recent research and developments related to patient-derived cancer models and their potential application in basic and translational cancer research.

Patient-derived cancer models, which faithfully reproduce the features of original tumors, have been pivotal tools in cancer research for more than a century. These models provide the data that determine our current understanding of cancer biology, including intriguing functions of novel genes and proteins which are aberrantly regulated in tumors. Well-created models reveal the molecular backgrounds of clinically important observations such as invasion, metastasis, and resistance against treatment. Established cancer research using these models has deepened our understanding of and provided novel therapy for cancers, and a considerable number of cancer models are banked and publicly available to researchers. Thus, patient-derived cancer models are undoubtedly the basis of cancer research. On the other hand, the principal of currently popular patient-derived cancer models was created in the mid-1900s, when our understanding of cancer was remarkably limited, and the fundamental ideas for these models have not considerably progressed since then. Moreover, although the predictive utility of patient-derived cancer models has been expected to facilitate clinical trials and realize precision medicine, their practical utility has not yet been established. Therefore, to cultivate innovative discovery, we need to improve upon the presently available models and challenge novel applications by considering modern technologies, clinical questions, current ideas in cancer biology, and the newest omics data.

The aim of this Special Issue is to collect reports concerning advances in patient-derived cancer models to drive researchers and clinicians towards innovative perspectives on basic and translational cancer research.

We look forward to your contributions to this Special Issue.

Dr. Tadashi Kondo
Prof. Dr. Noriko Gotoh
Dr. Yoshitaka Hippo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • patient-derived cancer models
  • cell line
  • organoid
  • spheroid
  • xenograft
  • preclinical models

Published Papers (5 papers)

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15 pages, 3238 KiB  
Article
Characterisation of a Novel Cell Line (ICR-SS-1) Established from a Patient-Derived Xenograft of Synovial Sarcoma
by William G. J. Kerrison, Jian Ning, Lukas Krasny, Amani Arthur, Nafia Guljar, Mark L. Elms, Amanda Swain, Robin L. Jones, Khin Thway and Paul H. Huang
Cells 2022, 11(15), 2418; https://doi.org/10.3390/cells11152418 - 04 Aug 2022
Cited by 1 | Viewed by 1882
Abstract
Synovial sarcoma is a rare translocation-driven cancer with poor survival outcomes, particularly in the advanced setting. Previous synovial sarcoma preclinical studies have relied on a small panel of cell lines which suffer from the limitation of genomic and phenotypic drift as a result [...] Read more.
Synovial sarcoma is a rare translocation-driven cancer with poor survival outcomes, particularly in the advanced setting. Previous synovial sarcoma preclinical studies have relied on a small panel of cell lines which suffer from the limitation of genomic and phenotypic drift as a result of being grown in culture for decades. Patient-derived xenografts (PDX) are a valuable tool for preclinical research as they retain many histopathological features of their originating human tumour; however, this approach is expensive, slow, and resource intensive, which hinders their utility in large-scale functional genomic and drug screens. To address some of these limitations, in this study, we have established and characterised a novel synovial sarcoma cell line, ICR-SS-1, which is derived from a PDX model and is amenable to high-throughput drug screens. We show that ICR-SS-1 grows readily in culture, retains the pathognomonic SS18::SSX1 fusion gene, and recapitulates the molecular features of human synovial sarcoma tumours as shown by proteomic profiling. Comparative analysis of drug response profiles with two other established synovial sarcoma cell lines (SYO-1 and HS-SY-II) finds that ICR-SS-1 harbours intrinsic resistance to doxorubicin and is sensitive to targeted inhibition of several oncogenic pathways including the PI3K-mTOR pathway. Collectively, our studies show that the ICR-SS-1 cell line model may be a valuable preclinical tool for studying the biology of anthracycline-resistant synovial sarcoma and identifying new salvage therapies following failure of doxorubicin. Full article
(This article belongs to the Special Issue Current Applications of Patient-Derived Cancer Model)
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13 pages, 4972 KiB  
Article
Establishment and Characterization of NCC-MFS5-C1: A Novel Patient-Derived Cell Line of Myxofibrosarcoma
by Ryuto Tsuchiya, Yuki Yoshimatsu, Rei Noguchi, Yooksil Sin, Takuya Ono, Taro Akiyama, Jun Sugaya, Eisuke Kobayashi, Naoki Kojima, Akihiko Yoshida, Seiji Ohtori, Akira Kawai and Tadashi Kondo
Cells 2022, 11(2), 207; https://doi.org/10.3390/cells11020207 - 08 Jan 2022
Cited by 4 | Viewed by 2057
Abstract
Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using [...] Read more.
Myxofibrosarcoma (MFS) is a highly aggressive malignancy with complex karyotypes and a postoperative recurrence tendency, owing to its strong invasiveness. Although systemic chemotherapy is considered in patients with unresectable MFS, the efficacy of conventional chemotherapy is hitherto unclear. Recently, drug screening analysis using a large number of tumor cell lines has been attempted to discover novel therapeutic candidate drugs for common cancers. However, the number of MFS cell lines is extremely small because of its low incidence—this hinders the conduction of screening studies and slows down the development of therapeutic drugs. To overcome this problem, we established a novel MFS cell line, NCC-MFS5-C1, which was shown to harbor typical MFS genetic abnormalities and thus had useful properties for in vitro studies. We conducted the largest integrated screening analysis of 210 drugs using NCC-MFS5-C1 cells along with four MFS cell lines, which we previously reported. Bortezomib (a proteasome inhibitor) and romidepsin (a histone deacetylase inhibitor) showed stronger antitumor effects than the standard drug, doxorubicin. Therefore, the NCC-MFS5-C1 cell line can potentially contribute to elucidating MFS pathogenesis and developing a novel MFS treatment. Full article
(This article belongs to the Special Issue Current Applications of Patient-Derived Cancer Model)
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23 pages, 5450 KiB  
Article
MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines
by Kristijan Skok, Lidija Gradišnik, Helena Čelešnik, Marko Milojević, Uroš Potočnik, Gregor Jezernik, Mario Gorenjak, Monika Sobočan, Iztok Takač, Rajko Kavalar and Uroš Maver
Cells 2022, 11(1), 117; https://doi.org/10.3390/cells11010117 - 30 Dec 2021
Cited by 3 | Viewed by 3014
Abstract
Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed [...] Read more.
Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage. Full article
(This article belongs to the Special Issue Current Applications of Patient-Derived Cancer Model)
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12 pages, 4421 KiB  
Article
The CAM Model for CIC-DUX4 Sarcoma and Its Potential Use for Precision Medicine
by Aoi Komatsu, Kotaro Matsumoto, Yuki Yoshimatsu, Yooksil Sin, Arisa Kubota, Tomoki Saito, Ayaka Mizumoto, Shinya Ohashi, Manabu Muto, Rei Noguchi, Tadashi Kondo and Fuyuhiko Tamanoi
Cells 2021, 10(10), 2613; https://doi.org/10.3390/cells10102613 - 01 Oct 2021
Cited by 9 | Viewed by 2752
Abstract
(1) Background: CIC-DUX4 sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there [...] Read more.
(1) Background: CIC-DUX4 sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there is a need to develop a model that mimics the features of each of these cancers. We evaluated the idea that the chicken chorioallantoic membrane assay (CAM), a convenient and versatile animal model, can be established for the CIC-DUX4 sarcoma. (2) Methods: Patient-derived cell lines of CIC-DUX4 were applied. These cells were transplanted onto the CAM membrane and tumor formation was examined by H&E staining, immunohistochemistry and Western blotting. The CAM tumor was transferred onto a fresh CAM and was also used to form organoids. Retention of the fusion gene was examined. (3) Results: H&E staining as well as molecular characterization demonstrated the formation of the CIC-DUX4 tumor on the CAM membrane. Expression of cyclin D2 and ETV4 was identified. The CAM tumor was transferred to a fresh CAM to form the second-generation CAM tumor. In addition, we were successful in forming tumor organoids using the CAM tumor. Retention of the fusion gene CIC-DUX4 in the CAM, second-generation CAM, and in the CAM-derived organoids was confirmed by RT-PCR. (4) Conclusions: The CAM assay provides a promising model for CIC-DUX4 sarcoma. Full article
(This article belongs to the Special Issue Current Applications of Patient-Derived Cancer Model)
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19 pages, 2116 KiB  
Systematic Review
Patient-Derived Xenotransplant of CNS Neoplasms in Zebrafish: A Systematic Review
by Beatriz E. Sarmiento, Santiago Callegari, Kemel A. Ghotme and Veronica Akle
Cells 2022, 11(7), 1204; https://doi.org/10.3390/cells11071204 - 02 Apr 2022
Cited by 4 | Viewed by 3452
Abstract
Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One [...] Read more.
Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor’s molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors. Full article
(This article belongs to the Special Issue Current Applications of Patient-Derived Cancer Model)
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