Final Report Summary - MYCINHIBINCLINIC (Pushing Myc inhibition towards the clinic)
The first approach turned out to be extremely efficient and proved a feasible strategy to treat Non-Small-Cell-Lung cancer (NSCLC) in vitro and in vivo. We characterized biophysically and biochemically the Omomyc peptide (OmomycCPP), which displayed very good cell penetrating properties, provided anti-Myc specific activity and displayed excellent therapeutic impact in NSCLC cells in culture, as well as in transgenic and xenograft mouse models of NSCLC. In these in vivo experimental models, OmomycCPP was administered either intranasally or intravenously and resulted in a significant reduction of tumor burden and grade, as a consequence of reduced tumor proliferation and increased death. Further development of the peptide towards its clinical application is now being carried out by a spin-off company from the laboratory, Peptomyc S.L.
The use of an intravenous peptide allowed for the expansion of our studies beyond NSCLC to additional indications, such as glioblastoma, triple negative breast cancer, melanoma, multiple myeloma, lymphoma, neuroblastoma and colorectal cancer. In all of them, we observed significant therapeutic impact.
Novel and improved variants of the original peptide have also been generated and validated in vitro and in vivo for future further development.
The second approach, based on anti-Myc small molecules, has demonstrated encouraging therapeutic impact only by some compounds in LSLKRasG12D transgenic mice, not necessarily due to Myc interference only. In fact, the molecules we tested in some cases suffered of relatively poor specificity, in other of poor bioavailability or even poor efficacy, requiring further optimization by their respective producing companies.
Overall the project advanced according to its predicted timeline and expanded beyond the initial proposed studies, to make Myc inhibition applicable to multiple types of cancer and eventually benefit a wide range of cancer patients.