This work had begun in earnest with the discovery that Myc overexpression is necessary for the hyper-vascular phenotype in simple xenograft models as well as in genetically complex cancers. This frequently occurs by a microRNA-dependent mechanism, through activation of the miR-17-92 cluster.
Subsequently, we demonstrated that in solid tumors, such as pediatric neuroblastoma and colon adenocarcinoma, deregulation of miR-17-92 leads to profound suppression of TGFβ signaling and diminished production of many anti-angiogenic TGFβ-inducible factors such as thrombospondin-1, CTGF, and clusterin. In fact, the MYC | miR-1792 and TGFβ pathways exhibit an epistatic relationship, where mutations in one pathway make mutations in the other redundant.
However, miR-17-92 is not the only pro-angiogenic microRNA. For example, colon cancer neovascularization also requires p53-regulated miR-194. Thus, targeting microRNAs might be a viable anti-angiogenic strategy, especially in tumors without VEGF overexpression.