Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer Publication date: 10 September 2019 Source: Cancer Letters, Volume 459 Author(s): Caroline Kreuzinger, Isabel von der Decken, Andrea Wolf, Magdalena Gamperl, Julia Koller, Jasmine Karacs, Stephanie Pfaffinger, Thomas Bartl, Alexander Reinthaller, Christoph Grimm, Christian F. Singer, Elena Ioana Braicu, Paula Cunnea, Charlie Gourley, Dominiek Smeets, Bram Boeckx, Diether Lambrechts, Paul Perco, Reinhard Horvat, Els M.J.J. Berns Abstract 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.