Obiettivo
The challenge for cancer therapy involves hampering the mechanisms by which the normal gene expression machinery is taken over to allow the aberrant appearance of cancer driving genes. I propose exploiting the therapeutic potential of a special class of tumor microRNAs (miRs) that function as natural post-transcriptional tumor suppressive regulators of many genes in key pathways. These anti-cancer effectors represent an inherent organismal property that I propose to augment and thereby translate into a form of systemic anti-cancer therapy. First, focusing on hepatocellular carcinoma (HCC), I shall perform high throughput screening to identify preferred HCC tumor suppressive miRs. Second, I shall search for small molecules capable of elevating the level of those relevant miRs in tumor cells and tissues. Increasing miR expression will potentially also enhance their secretion into the circulation in exosomes thereby suppressing gene expression at remote tissue sites as well. Third, I shall test the potential of these miRs to better target and inhibit the growth of tumor cells both, in culture and in vivo. This unprecedented conceptual strategy should stimulate the organism’s self-healing potential by enhancing inherent anti-tumor mechanisms. This project is built on robust preliminary findings that show promiscuous anti-cancer effects and predictably fewer side effects due to its completely host-based nature, with the administered miR inducer being the only foreign element. Additionally, due to the fact that each miR simultaneously targets a number of molecular pathways as well as multiple steps within a given pathway, it could help to overcome the major problem of cancer therapy – resistance. This strategy of harnessing these efficient and robust miRs and exosomes for delivery of anti-cancer therapeutics may overcome the high-risk challenge involved and enable high gain value.
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Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
91904 Jerusalem
Israele