Academic Journal
Preclinical patient‐derived modeling of castration‐resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease
| Τίτλος: | Preclinical patient‐derived modeling of castration‐resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease |
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| Συγγραφείς: | Mohamed E. Elsesy, Su Jung Oh‐Hohenhorst, Christoph Oing, Alicia Eckhardt, Susanne Burdak‐Rothkamm, Malik Alawi, Christian Müller, Ulrich Schüller, Tobias Maurer, Gunhild von Amsberg, Cordula Petersen, Kai Rothkamm, Wael Mansour |
| Πηγή: | Mol Oncol Molecular Oncology, Vol 17, Iss 6, Pp 1129-1147 (2023) |
| Στοιχεία εκδότη: | Wiley, 2023. |
| Έτος έκδοσης: | 2023 |
| Θεματικοί όροι: | castration‐resistant prostate cancer, Male, Pulmonary and Respiratory Medicine, 0301 basic medicine, DNA Repair, homologous recombination, Cancer research, Gene, 03 medical and health sciences, Advancements in Prostate Cancer Research, Olaparib, Biochemistry, Genetics and Molecular Biology, Health Sciences, In vivo, Genetics, Humans, Poly(ADP-ribose) Polymerase Inhibition in Cancer Therapy, Chemotherapy, Homologous recombination, Molecular Biology, Internal medicine, Biology, RC254-282, Research Articles, Cancer, 0303 health sciences, Prostate cancer, PARP inhibition, Prostate Cancer, ex vivo tumor cultures, LNCaP, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Recombinational DNA Repair, Life Sciences, 3. Good health, Molecular Mechanisms of DNA Damage Response, Ex vivo, Prostatic Neoplasms, Castration-Resistant, PARP inhibitor, Oncology, patient‐derived organoids, FOS: Biological sciences, Medicine, RAD51, Poly ADP ribose polymerase, Cisplatin, Polymerase |
| Περιγραφή: | The use of mutation analysis of homologous recombination repair (HRR) genes to estimate PARP‐inhibition response may miss a larger proportion of responding patients. Here, we provide preclinical models for castration‐resistant prostate cancer (CRPC) that can be used to functionally predict HRR defects. In vitro, CRPC LNCaP sublines revealed an HRR defect and enhanced sensitivity to olaparib and cisplatin due to impaired RAD51 expression and recruitment. Ex vivo‐induced castration‐resistant tumor slice cultures or tumor slice cultures derived directly from CRPC patients showed increased olaparib‐ or cisplatin‐associated enhancement of residual radiation‐induced γH2AX/53BP1 foci. We established patient‐derived tumor organoids (PDOs) from CRPC patients. These PDOs are morphologically similar to their primary tumors and genetically clustered with prostate cancer but not with normal prostate or other tumor entities. Using these PDOs, we functionally confirmed the enhanced sensitivity of CRPC patients to olaparib and cisplatin. Moreover, olaparib but not cisplatin significantly decreased the migration rate in CRPC cells. Collectively, we present robust patient‐derived preclinical models for CRPC that recapitulate the features of their primary tumors and enable individualized drug screening, allowing translation of treatment sensitivities into tailored clinical therapy recommendations. |
| Τύπος εγγράφου: | Article Other literature type |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | English |
| ISSN: | 1878-0261 1574-7891 |
| DOI: | 10.1002/1878-0261.13382 |
| DOI: | 10.60692/vjm1g-tpr82 |
| DOI: | 10.60692/6c32v-tvr74 |
| Σύνδεσμος πρόσβασης: | https://pubmed.ncbi.nlm.nih.gov/36694344 https://doaj.org/article/de640423cfee4a5e9ddaf1dec52ce8c8 |
| Rights: | CC BY |
| Αριθμός Καταχώρησης: | edsair.doi.dedup.....b9379b8bccb8e4f6438d0ed90ace9df1 |
| Βάση Δεδομένων: | OpenAIRE |
| ISSN: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13382 |