The non-canonical activation is thought to have an important role in RMS, since there is solid evidence that several pathways (especially PI3K/AKT/mTOR and RAS/MEK/ERK) can promote GLI protein activation in this particular type of cancer, thereby suggesting the possibility of using combined therapies which putatively may benefit patients with refractory tumours or even tumours that develop resistance after receiving Hh monotherapy. This evidence concerns the gene GLI1 and cancer.