Hedgehog信号通路及其抑制剂在癌症中的研究进展

Research progress of Hedgehog signaling pathway and its inhibitors in cancers

Hedgehog(HH)信号通路在胚胎发育和器官形成中发挥重要作用。当该通路中成员发生异常如patched(PTCH)发生缺失或突变,smoothened(SMO)发生突变,Gli异常扩增或者蛋白质稳定性增加等,都会导致该通路异常激活,并诱导如基底细胞癌、成神经管细胞瘤等癌症发生。因此阻断HH信号通路是应用于癌症治疗的一个有效手段。目前以HH信号通路不同成员为靶点已开发出多种HH信号通路小分子抑制剂,其中以HH信号通路上游成员为靶点的抑制剂最多。在今后的研究中,应该更加注重于以HH信号通路下游为靶点,开发更加有效的抗癌药物。

The Hedgehog （HH） pathway is a conserved signaling pathway essential for embryonic development and organ formation. It can be abnormally activated by the loss or mutation of Patched （PTCH）, mutation of Smoothened （SMO）, or abnormal amplification of Glil and increased Glil protein stability, resulting in the occurrence of cancers, such as basal cell carcinoma and medulloblastoma. Thus targeting elements of the HH pathway may offer an effective therapeutic strategy in the fight against certain cancers. Many small-molecule inhibitors that target different components of the HH pathway have already been discovered, and most of these seem to target elements upstream of the HH pathway. The search for small molecules that may target elements downstream of the HH pathway and their development into potential and effective anti-cancer drugs may constitute a major part of future research into HH signaling.