ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2022
Phenotypical screening on metastatic PRCC-TFE3 fusion translocation renal cell carcinoma organoids reveals potential therapeutic agents.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- Harnessing organoid technology in urological cancer: advances and applications in urinary system tumors.World journal of surgical oncology · 2025Review
- Organoids as Sophisticated Tools for Renal Cancer Research: Extensive Applications and Promising Prospects.Cellular and molecular bioengineering · 2024Review
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- The potential of organoids in renal cell carcinoma research.BMC urology · 2024Review
- Construction methods and latest applications of kidney cancer organoids.Oncology reviews · 2024Review
- High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Establishment of a ccRCC patient-derived chick chorioallantoic membrane model for drug testing.Frontiers in medicine · 2022Article
- SAE1 May Play a Pro-Carcinogenic Role in Pancreatic Adenocarcinoma: A Comprehensive Study Integrating Multiple Pieces of Evidence.IET systems biologyArticle
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10 authors at 2 institutions in 2 countries.
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Abstract
purposeTranslocation renal cell carcinoma (tRCC) is a subtype that occurs predominantly in children and young individuals. Metastatic tRCC occurring in young patients is more aggressive than that occurring in older patients, and there are still no effective therapies. Organoids can mimic original tissues and be assessed by high-throughput screening (HTS). We aimed to utilize patient-derived organoids and HTS to screen drugs that can be repurposed for metastatic tRCC with PRCC-TFE3 fusion.
methodsTumor tissues were obtained from treatment-naïve metastatic tRCC patients who underwent surgery. Histopathology and fluorescence in situ hybridization (FISH) confirmed the tRCC. Organoids derived from the dissected tissues were cultured and verified by FISH and RNA-seq. HTS was performed to seek promising drugs, and potential mechanisms were explored by RNA-seq and cell-based studies.
resultsWe successfully established a metastatic tRCC organoid with PRCC-TFE3 fusion, a common fusion subtype, and its characteristics were verified by histopathology, FISH, and RNA-seq. An HTS assay was developed, and the robustness was confirmed. A compound library of 1816 drugs was screened. Eventually, axitinib, crizotinib, and JQ-1 were selected for further validation and were found to induce cell cycle arrest and apoptosis. RNA-seq analyses of posttreatment organoids indicated that crizotinib induced significant changes in autophagy-related genes, consistent with the potential pathogenesis of tRCC.
conclusionsWe established and validated organoids derived from tissues dissected from a patient with metastatic tRCC with PRCC-TFE3 fusion and achieved the HTS process for the first time. Crizotinib might be a targeted therapy worthy of exploration in the clinic for metastatic tRCC with PRCC-TFE3 fusion. Such organoid and HTS assays may represent a promising model system in translational research assisting in the development of clinical strategies.
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