Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.

ABSTRACT: Hedgehog (Hh) signaling is a highly conserved pathway that plays a vital role during embryonic development. Recently, uncontrolled activation of this pathway has been demonstrated in various types of cancer. Therefore, Hh pathway inhibitors have emerged as an important class of anti-cancer agents. Unfortunately, however, their reputation has been tarnished by the emergence of resistance during therapy, necessitating clarification of mechanisms underlying the drug resistance. In this review, we briefly overview canonical and non-canonical Hh pathways and their inhibitors as targeted cancer therapy. In addition, we summarize the mechanisms of resistance to Smoothened (SMO) inhibitors, including point mutations of the drug binding pocket or downstream molecules of SMO, and non-canonical mecha

SUBMITTER: Nguyen NM 

PROVIDER: S-EPMC8835893 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature