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- W2287148461 abstract "Background In the last three decades the outcome for patients with localised Ewing sarcoma (ES) has improved significantly since the introduction of multimodality primary treatment. However, for patients with (extra-) pulmonary metastatic and/or non-resectable relapsed disease the outcome remains poor and new treatment options are urgently needed. Currently the insulin-like growth factor 1 receptor (IGF-1R) pathway and the poly-ADP(adenosinediphosphate)-ribose-polymerase (PARP) pathway are being investigated for potential targeted therapies. IGF-1R The IGF-1R pathway is known to be deregulated by the EWSR1-FLI1 translocation which makes it a potential target for therapy. Clinical trials have been reported in which only ES patients were treated with an IGF-1R inhibitor, either as single agent or in combination. In total 291 ES patients were included in these trials, in which two (0.7%) complete responses, 32 (11%) partial responses of which some durable, and 61 (21%) stable diseases were observed. PARP In the presence of a PARP inhibitor DNA strand breaks cannot be efficiently repaired, leading to cell death. The first phase II trial with ES patients was recently published and showed no clinical responses, which may have been due to the drug being non-effective as a single agent. Discussion The IGF-1R pathway is an interesting target for ES and should be explored further, as biomarkers to select patients that might benefit from treatment are lacking. PARP inhibitors as single agent have so far failed to show improvement in outcome. Future directions include dual insulin receptor/IGF-1R blockade with linsitinib as well as chemotherapy–PARP combinations. Both therapeutic strategies are currently being explored." @default.
- W2287148461 created "2016-06-24" @default.
- W2287148461 creator A5003014435 @default.
- W2287148461 creator A5007411490 @default.
- W2287148461 creator A5025935523 @default.
- W2287148461 creator A5048987054 @default.
- W2287148461 creator A5083401778 @default.
- W2287148461 date "2016-01-01" @default.
- W2287148461 modified "2023-10-16" @default.
- W2287148461 title "Ewing sarcoma: The clinical relevance of the insulin-like growth factor 1 and the poly-ADP-ribose-polymerase pathway" @default.
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