SUMMARY

The ideal cancer drug should target a signaling conduit common to multiple cancer types, be both non-redundant and also necessary for tumor maintenance, as well as dispensable for normal tissue function. In the search for this ideal target our group focuses on the pleiotropic and ubiquitous Myc oncoprotein, whose deregulation is implicated in almost all human cancers. The technical challenges of targeting nuclear transcription factors such as Myc – and the concern regarding potential side effects – had until recently precluded any preclinical validation of Myc inhibition as a possible therapeutic approach. However, over the past few years, we have demonstrated in several mouse models that Myc inhibition has a dramatic therapeutic impact across several tumor types, with very mild and reversible side effects in normal tissue.
We are currently extending our studies to the notoriously difficult to treat cancers that are currently resistant to standard therapy and are in dire need of new therapeutic options (i.e. KRas driven Non Small Cell Lung Cancer, glioblastoma, metastatic breast cancer). Glioblastoma in particular has been the focus of our recently published study in Nature Communications (Annibali et al., Nat Commun. 2014), in which we demonstrated that Myc inhibition would be a valuable therapeutic approach by causing mitotic catastrophe, arrest and death of cancer cells.

Encouraged by our results in mouse models, we are now interested in developing viable, non-toxic pharmacological options for Myc targeting in the clinic. In this context, this year we obtained a prestigious European Research Council (ERC) Consolidator Grant, to develop, produce and purify Omomyc-based cell penetrating peptides for direct delivery to cancer cells and tumors. Studies assessing their therapeutic impact are currently underway.

PUBLICATIONS