Milea Timbergen

27 Table 1. Overview of drugs used in vitro / vivo studies targeting a signalling pathway in DTF Drug Ref. Setting Effect Wnt/ß-catenin signalling pathway MMP inhibitor Ilomastat /Galardin (GM6001) 52 Apc + /Apc 1638N mice Murine PCC from DTF and NF ↓ DTF cell invasion and motility ↓ tumour volume in mice 53 Human PCC from DTF and normal fascia (n=7) ↔ cell growth ↓ DTF cell invasion Human PCC from DTF and normal marginal tissues Apc + /Apc 1638N -Cox2 -/- and Apc + /Apc 1638N - Cox2 +/+ mice ↓ DTF cell and NF proliferation ↔ apoptosis in DTF cells and NF ↔ tumour number in mice (sulindac) ↓ tumour volume in mice (sulindac) NSAID Sulindac / Indomethacin / DFU 56 Human PCC from DTF and normal marginal tissues Apc + /Apc 1638N -Cox2 -/- and Apc + /Apc 1638N - Cox2 +/+ mice ↓ DTF cell and NF proliferation ↔ apoptosis in DTF cells and NF ↔ tumour number in mice (sulindac) ↓ tumour volume in mice (sulindac) NSAID Sulindac 57 Human PCC from DTF,CRC ↓ DTF cell growth ↔ cell morphology NSAID Piroxicam (+DFMO) 58 Apc -/+ p53 +/- , Apc +/+ p53 +/- , Apc -/+ p53 +/+ mice ↓ DTF tumour number Angiostatic factor Endostatin 59 Human PCC from FAP- related DTF and CRC ↑ apoptosis (CRC cultures) ↑ cell death (DTF cultures) Benzoxazocine Nefopam 60 Human PCC from DTF and NF Apc 1638N mice ↓ cell proliferation, modest change in apoptosis ↓ ß-catenin protein level ↓ tumour number and volume (mice) Hedgehog signalling pathway Hedgehog inhibitor Triparanol 61 Human PCC from DTF Apc +/1638N ; Gli2 +/- and Apc +/1638N ; Gli2 +/+ mice ↓ tumour volume ( Apc +/1638N mice) ↓ number of tumours ( Apc +/1638N ; Gli2 +/- ) ↓ number of tumour cells, viability, proliferation rate (DTF cells) ↔ apoptosis (DTF cells) Notch signalling pathway ɣ-secretase inhibitor PF-03084014 62 Human PCC from DTF ↓ Notch signalling (↓ NICD and Hes1 expression) ↑ cell cycle arrest ↓ cell growth, migration and invasion JAK/STAT signalling pathway Cytokines Interferon-ß 63 Human PCC from DTF and NF Apc/Apc 1638N , A pc 1638N ; Ifnar1 -/- and Apc/Apc 1638N ; Ifnar1 +/+ ↔ apoptosis (human vs. murine DTF and NF) ↓ cell proliferation (human/ murine DTF and NF) 2