Milea Timbergen

32 Table 2. (continued) Drug Ref. Setting Tumour type N of DTF patients Efficacy in DTF Sunitinib 85 Phase 2 Non-GIST sarcomas (n = 53) 1 DTF patients: n = 1 NR 86 Phase 2 advanced DTF 19 Median FU 20.3 months (1.8-50.7 months), 2-year PFS 74.7%, OS 94.4%. n = 5 PR, n = 8 SD, n = 3 PD, n = 3 not evaluable. Median duration of the response 8.2 months (range 2.0-17.3 months) Sorafenib (+ topotecan)87 Phase 1 Paediatric solid malignancies (n = 13) 2 DTF patients: n = 1 PR 88 Phase 3 Advanced and refractory DTF 87 2-year PFS of sorafenib 81% (95%CI 69-96%) vs. placebo 36% (95%CI 22-57%) ORR of sorafenib 33% (95% CI 20-48%) vs. placebo 20% (95% CI 8-38%) Oestrogen driven pathway Anti-oestrogen + NSAID Tamoxifen + sulindac 89 Phase 2 Paediatric DTF 59 n = 4 PR, n = 1 CR 2-year PFS 36%, OS 96% CI, confidence interval; CR, complete response; DTF, desmoid-type fibromatosis; GIST, gastro-intestinal stromal tumour; N, number of patients; NPRR, non-progressive response rate; NR, no response; ORR, objective response rate; ORS, overall response rate, OS, overall survival; PAR, progression arrest rate; PD, progressive disease; PFS, progression free survival; PR, partial response; SD, stable disease; TS, treatment stop; TTF, time to treatment failure; TTP, Time to progression; TTR, time to recurrence The Hedgehog signalling pathway in desmoid-type fibromatosis The Hedgehog signalling pathway The Hedgehog (Hh) signalling pathway plays an essential role in embryonic development, in adult tissue homeostasis, tissue renewal and tissue regeneration. Precursor proteins of Hh ligands, including Sonic (Shh), Indian (Ihh) and Desert (Dhh), undergo autocatalytic cleavage and cholesterol alterations at the carboxy terminal end, and palmitoylation at their amino terminal end. This process results in a dually-lipidated protein, which is released from the secreting cell surface. Subsequently, the Hh ligands interact with cell surface proteins like Glypican and the proteins of the of heparin sulfate proteoglycan family 2