Small molecule modulation of HH-GLI signaling: Current leads, trials and tribulations

Many human sporadic cancers have been recently shown to require the activity of the Hedgehog-GLI pathway for sustained growth. The survival and expansion of cancer stem cells is also HH-GLI dependent. Here we review the advances on the modulation of HH-GLI signaling by small molecules. We focus on both natural compounds and synthetic molecules that target upstream pathway components, mostly SMOOTHENED, and those that target the last steps of the...