WNT and Notch pathways have been obviously demonstrated to participate in the OS development 10,81,82
Hedgehog and Notch pathways have been also contributed in to the perivascular niche, which VEGF/VEGFR axis and SDF-1(CXCL12) CXCR4 axis has been associated with reprograming and angiogenic process in endothelial cells. Therefore, it is noteworthy that VEGF and CXCR4 inhibitors also play an important role in inhibiting angiogennic process, where perivascular niche could be broken down 4
An increase in drugs sensitization was previously observed when NOTCH and WNT pathways were inhibited in OS cell lines 83. It is worth noting that DKK1(Dickkopf-related protein 1) as enhancer of protumorigenic features is able to suppress the canonical WNT pathway, where is linked to noncanonical JUN-mediated WNT pathways, and can consequently play a key role in mediating tumorigenic potential, partly, by ALDH1A1 and tress response enzyme overexpression.