Patient-derived xenografts and organoids model therapy response in prostate cancer
| العنوان: | Patient-derived xenografts and organoids model therapy response in prostate cancer |
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| المؤلفون: | Marco Bolis, Arianna Vallerga, Salvatore Piscuoglio, Andrej Benjak, Andrea Sboner, Federico La Manna, Mirjam Kiener, Joel Grosjean, Tijmen H. Booij, David Keller, Charlotte K.Y. Ng, Eugenio Zoni, Martin Spahn, Vera Genitsch, Sofia Karkampouna, Irena Klima, Mark A. Rubin, Kenneth Eng, Marianna Kruithof-de Julio, Christian U. Stirnimann, Jean-Philippe Theurillat, Andrea Garofoli, Maria R. De Filippo, Marta De Menna, George N. Thalmann, Peter C. Gray |
| المصدر: | Nature Communications Karkampouna, Sofia; La Manna, Federico; Benjak, Andrej; Kiener, Mirjam; De Menna, Marta; Zoni, Eugenio; Grosjean, Joël; Klima, Irena; Garofoli, Andrea; Bolis, Marco; Vallerga, Arianna; Theurillat, Jean-Philippe; De Filippo, Maria R.; Genitsch, Vera; Keller, David; Booij, Tijmen H; Stirnimann, Christian U; Eng, Kenneth; Sboner, Andrea; Ng, Kiu Yan Charlotte; ... (2021). Patient-derived xenografts and organoids model therapy response in prostate cancer. Nature communications, 12(1), p. 1117. 10.1038/s41467-021-21300-6 <http://dx.doi.org/10.1038/s41467-021-21300-6> Nature Communications, 12(1). NATURE RESEARCH Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications, 12 (1) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Sorafenib, Male, Science, Medizin, General Physics and Astronomy, 610 Medicine & health, Antineoplastic Agents, SPOP, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, Cancer screening, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, medicine, Organoid, Humans, Neoplasm Metastasis, Cancer models, Multidisciplinary, Sunitinib, business.industry, Genome, Human, Cancer stem cells, Ponatinib, Microsatellite instability, Prostatic Neoplasms, General Chemistry, medicine.disease, Primary tumor, Xenograft Model Antitumor Assays, 3. Good health, Organoids, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Mutation, Cancer research, Androgens, 570 Life sciences, biology, business, Transcriptome, medicine.drug |
| الوصف: | Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor. PNPCa harbors BRCA2 and CHD1 somatic mutations, shows an SPOP/FOXA1-like transcriptomic signature and microsatellite instability, which occurs in 3% of advanced PCa and has never been modeled in vivo. Comparison of the treatment-naïve PNPCa with additional metastatic PDXs (BM18, LAPC9), in a medium-throughput organoid screen of FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX- and patient-derived organoids from advanced cases with acquired resistance to standard-of-care compounds. This proof-of-principle study may provide a preclinical tool to screen drug responses to standard-of-care and newly identified, repurposed compounds. To date, patients still succumb to cancer, due to tumors not responding to therapy or ultimately acquiring resistance. Here the authors show that by exploiting patient derived organoids and a treatment-naïve patient derived xenograft, patient therapy can be personalized. |
| وصف الملف: | application/pdf; application/application/pdf |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::117825a87909e4c096c1384627ad7d36 https://pubmed.ncbi.nlm.nih.gov/33602919 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....117825a87909e4c096c1384627ad7d36 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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