For example, the γ-secretase inhibitor RO4929097 in Notch blockade therapy and the Hedgehog pathway inhibitor vismodegib displayed little effect in phase II trials.498,499 The limited progress of anti-TGF-β and anti-Wnt therapy against CRC has also been reviewed.500,501 Agents such as COX-2 inhibitors were found to be helpful in CRC prevention in terms of Wnt inhibition; however, the development of other agents that might enhance chemotherapy sensitivity, yet direct CRC-control-targeted drugs with high affinity to single targets, still lags behind. The gene discussed is TGFB1; the disease is colorectal carcinoma.