<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines"^^ . "Poly(ADP-ribose) polymerase inhibitors (PARPis) have exhibited significant efficacy in clinical\r\nsettings and thus shown promise as a therapeutic option for ovarian cancer patients with\r\nBRCA mutations. However, the emergence of resistance to PARPis poses a substantial\r\nchallenge, limiting its long-term effectiveness. Consequently, understanding additional\r\nresistance mechanisms is crucial to improve the treatment efficacy of PARPis.\r\nIn this thesis, I utilized patient-derived ovarian cancer cell lines initially screened for their\r\nresponse to PARPi treatment. To induce resistance, the two most responsive cell lines were\r\nsubjected to multiple rounds of increasing concentrations of olaparib (the first approved\r\nPARPi) treatment. Notably, both cell lines were Homologous Recombination (HR)-proficient,\r\nmaking them theoretically unsuitable for PARPi treatment. Employing various molecular and\r\nsequencing approaches, I investigated and characterized the acquired PARPi resistance\r\nmechanism in these HR-proficient ovarian cancer cell lines.\r\nSurprisingly, I did not detect a known resistance mechanism to PARPis, possibly due to the HR\r\nproficiency of both resistant and sensitive cells. However, the olaparib-resistant cell lines\r\ndemonstrated cross-resistance to other PARPis (Pamiparib, Niraparib, Rucaparib, Talazoparib)\r\nwhile remaining sensitive to DNA-damaging agents, suggesting a PARP-specific and DNA\r\nrepair-independent resistance mechanism. Yet, the precise mechanism underlying acquired\r\nresistance to PARPis in both cell lines remains to be determined. Nonetheless, the observation\r\nthat HR-proficient cell lines can be susceptible to PARPi treatment may expand the potential\r\ntreatment scope of PARPis to patients traditionally excluded based on their HR status.\r\nIn summary, this study demonstrates that some HR-proficient cells can be vulnerable to PARPi\r\ntreatment and that the acquired resistance in these cell lines is independent of DNA repair\r\npathways."^^ . "2024" . . . . . . . "Jonas Norbert"^^ . "Schwickert"^^ . "Jonas Norbert Schwickert"^^ . . . . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (PDF)"^^ . . . "Thesis Jonas Schwickert final.pdf"^^ . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Characterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #34627 \n\nCharacterization of PARP inhibitor resistance in patient-derived ovarian cancer cell lines\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .