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• W2890987715 abstract "5578 Background: Patients with High Grade Serous Ovarian Cancer (HGSOC) initially respond to SOC platinum based treatment but most will eventually relapse with platinum resistant disease. Angiogenesis is known to be an integral pathological feature of HGSOC and anti-angiogenic agents have been trialed in this population, but have failed to demonstrate a significant impact on overall survival (OS). Here, we asked if platinum resistance could be associated with an improved response to anti-angiogenic therapies. Methods: A meta-analysis of 14 phase II and III clinical trials in EOC were used to investigate the association between platinum resistance and response to anti-angiogenic agents. In addition we analysed gene expression in 12 matched pre-and post-chemotherapy samples. Novel cisplatin-resistant HGSOC cell lines and novel ascites-derived primary cell lines from HGSOC patients with known outcomes following platinum-based chemotherapy were developed to investigate the relationship between angiogenesis and platinum resistance. Results: The meta-analysis revealed an OS benefit for anti-angiogenics in platinum-resistant disease (p = 0.029), whilst platinum-sensitive disease derived only PFS benefit (p = < 0.0001). In the matched pairs of patient samples, post-platinum samples had a higher micro-vessel density (MVD) relative to their paired treatment-naïve sample (p = 0.0001). Additionally, an in vivo angiogenesis matrigel plug assay demonstrated that cisplatin-resistant EOC cell lines were associated with an increase in MVD (p = < 0.0001). MVD was reduced in the platinum-resistant cells following treatment with bevacizumab (p = 0.001). Ascites-derived cells established from platinum-resistant patients demonstrated overexpression of VEGF-A through increased PDGFRa and PDGFRb expression. Conclusions: We have demonstrated that previous platinum therapy for EOC is associated with an increase in tumour PDGFα and VEGF-A expression, correlating with a response to anti-angiogenic therapies. This data suggests that platinum therapy resistance may inform the selection of EOC patients for novel anti-angiogenic therapies in future clinical trials." @default.
• W2890987715 created "2018-09-27" @default.
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• W2890987715 date "2018-05-20" @default.
• W2890987715 modified "2023-10-14" @default.
• W2890987715 title "Platinum based chemotherapy selects for PDGFRα dependent angiogenesis." @default.
• W2890987715 doi "https://doi.org/10.1200/jco.2018.36.15_suppl.5578" @default.
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