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Preclinical investigation of patient- derived cervical cancer organoids for precision medicine
설향숙,오주희,최은혜,김상민,김현기,Eun Ji Nam 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.3
Objective: Advanced cervical cancer is still difficult to treat and in the case of recurrent cancer, it is desirable to utilize personalized treatment rather than uniform treatment because the type of recurrence is different for each individual. Therefore, this study aimed to establish a patient-derived organoid (PDO) platform to determine the effects of chemotherapy, radiation therapy, and targeted therapy in cervical cancer. Methods: We established organoids from 4 patients with various types of cervical cancer. The histopathological and gene profiles of these organoid models were compared to determine their characteristics and the maintenance of the patient phenotype. Each type of organoid was also subjected to anticancer drug screening and radiation therapy to evaluate its sensitivity. Results: We established PDOs to recapitulate the main elements of the original patient tumors, including the DNA copy number and mutational profile. We selected 7 drugs that showed growth inhibition in cervical cancer organoids out of 171 using an Food and Drug Administration -approved drug library. Moreover, adenocarcinoma and large-cell neuroendocrine carcinoma showed resistance to radiation therapy. whereas squamous cell carcinoma and villoglandular carcinoma showed a significant response to radiotherapy. Conclusion: Our results showed that patient-derived cervical cancer organoids can be used as a platform for drug and radiation sensitivity testing. These findings suggest that patient-derived cervical cancer organoids could be used as a personalized medicine platform and may provide the best treatment options for patients with various subtypes of cervical cancer.
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설향숙(Hyang Sook Seol),장인호(In Ho Chang) 대한비뇨기종양학회 2020 대한비뇨기종양학회지 Vol.18 No.2
Bladder cancer, which affects the bladder mucosa, is the ninth most common disease worldwide. There are many types of cancerous tissue in the bladder. Most exhibit low malignancy, but their recurrence rate is higher in comparison to more malignant tissues. Only 10%-15% progress to invasive bladder cancer and metastasize to the lung, liver, and bone, which is significantly difficult to treat. The anticancer efficacy developed for the treatment of highly malignant bladder cancer does not equally apply to all patients, and the side effects vary. To solve this problem, studies have been conducted on various verification systems and patient-specific drug development. For example, an organ-on-a-chip model using patient cancer cells is being actively researched as an anticancer drug verification system. A study on screening anticancer drugs according to cancer biomarkers unique to individual patients is also in progress. In addition, studies have recently been conducted on immune anticancer drugs that exhibit excellent anticancer efficacy. This report discusses various validation systems and drug screening criteria for the development of patient-specific drugs. We propose that it is possible to evaluate the efficacy of anticancer drugs for each patient, understand drug mechanism patterns in humans, and develop treatment that prevents cancer metastasis.
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강효정,설향숙,이상은,서영아,김지훈,장세진,유은실 대한병리학회 2019 Journal of Pathology and Translational Medicine Vol.53 No.2
Background: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patientderived preclinical models may facilitate drug discovery for HCC patients. Methods: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. Results: Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. Conclusions: Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.
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The Generation and Application of Patient-Derived Xenograft Model for Cancer Research
정재윤,설향숙,장수환 대한암학회 2018 Cancer Research and Treatment Vol.50 No.1
Establishing an appropriate preclinical model is crucial for translational cancer research. The most common way that has been adopted by far is grafting cancer cell lines, derived from patients. Although this xenograft model is easy to generate, but has several limitations because this cancer model could not represent the unique features of each cancer patient sufficiently. Moreover, accumulating evidences demonstrate cancer is a highly heterogeneous disease so that a tumor is comprised of cancer cells with diverse characteristics. In attempt to avoid these discrepancies between xenograft model and patients’ tumor, a patient-derived xenograft (PDX) model has been actively generated and applied. The PDX model can be developed by the implantation of cancerous tissue from a patient’s tumor into an immune-deficient mouse directly, thereby it preserves both cell-cell interactions and tumor microenvironment. In addition, the PDX model has shown advantages as a preclinical model in drug screening, biomarker development and co-clinical trial. In this review, we will summarize the methodology and applications of PDX in detail, and cover critical issues for the development of this model for preclinical research.
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