Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer
| Autor: | Diether Lambrechts, Reinhard Horvat, Dominiek Smeets, Jasmine Karacs, Bram Boeckx, Charlie Gourley, Els M.J.J. Berns, Elena Ioana Braicu, Dan Cacsire Castillo-Tong, Christian F. Singer, Magdalena Gamperl, Stephanie Pfaffinger, Paul Perco, Caroline Kreuzinger, Andrea Wolf, Alexander Reinthaller, Paula Cunnea, Thomas Bartl, Julia Koller, Isabel von der Decken, Christoph Grimm |
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| Přispěvatelé: | Medical Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_treatment Estrogen receptor MELANOMA medicine.disease_cause Carboplatin 0302 clinical medicine Serous ovarian cancer Acquired platinum resistance TP53 Molecular Targeted Therapy Aged 80 and over Ovarian Neoplasms Cell Cycle Middle Aged 3. Good health Oncology Receptors Estrogen 030220 oncology & carcinogenesis Disease Progression Female Life Sciences & Biomedicine Adult Cyclin-Dependent Kinase Inhibitor p21 ANTIGEN p21 down-regulation 03 medical and health sciences Antigen SDG 3 - Good Health and Well-being Antigens Neoplasm PRAME Cell Line Tumor medicine Humans Aged Chemotherapy Science & Technology business.industry medicine.disease Cystadenocarcinoma Serous 030104 developmental biology Tumor specific antigen Cell culture Drug Resistance Neoplasm Cancer research Drug Screening Assays Antitumor Neoplasm Grading Tumor Suppressor Protein p53 Ovarian cancer business Carcinogenesis EXPRESSION ANALYSIS |
| Zdroj: | Kreuzinger, C, von der Decken, I, Wolf, A, Gamperl, M, Koller, J, Karacs, J, Pfaffinger, S, Bartl, T, Reinthaller, A, Grimm, C, F Singer, C, Ioana Braicu, E, Cunnea, P, Gourley, C, Smeets, D, Boeckx, B, Lambrechts, D, Perco, P, Horvat, R, M.J.J. Berns, E & Cacsire Castillo-Tong, D 2019, ' Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer ', Cancer letters . https://doi.org/10.1016/j.canlet.2019.05.032 Cancer Letters, 459, 1-12. Elsevier Ireland Ltd |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2019.05.032 |
| Popis: | High grade serous ovarian cancer (HGSOC) is the most frequent type of ovarian cancer. Most patients have primary response to platinum-based chemotherapy but frequently relapse, which leads to patient death. A lack of well documented and characterized patient-derived HGSOC cell lines is so far a major barrier to define tumor specific therapeutic targets and to study the molecular mechanisms underlying disease progression. We established 34 patient-derived HGSOC cell lines and characterized them at cellular and molecular level. Particularly, we demonstrated that a cancer-testis antigen PRAME and Estrogen Receptor could serve as therapeutic targets. Notably, data from the cell lines did not demonstrate acquired resistance due to tumor recurrence that matched with clinical observations. Finally, we presented that all HGSOC had no or very low CDKN1A (p21) expression due to loss of wild-type TP53, suggesting that loss of cell cycle control is the determinant for tumorigenesis and progression. In conclusion, patient-derived cell lines reveal that PRAME is a potential tumor specific therapeutic target in HGSOC and counteracting the down-regulation of p21 caused by loss of wild-type TP53 might be the key to impede disease progression. ispartof: CANCER LETTERS vol:459 pages:1-12 ispartof: location:Ireland status: published |
| Databáze: | OpenAIRE |
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