Taken together, these findings suggest a therapeutic approach for targeting MYC-dependent cancers and provide the framework for the ongoing clinical studies addressing the efficacy of MUC1-C inhibition in solid tumors.
Oncogene amplification resulting in aberrant expression, although common in solid tumors, is rare in acute myeloid leukemia (AML) and is mostly associated with amplification of MYC, RUNX1, and MLL genes.
AVI-4126, a neutral antisense phosphorodiamidate morpholino oligomer (PMO) has been identified to specifically inhibit c-MYC expression in multiple disease models and identified in Phase I clinical studies to be safe and bioavailable in solid tumors.
Our results suggest that genetic rearrangements, in addition to an increased C-MYC copy number, may be a mechanism of MYC oncogene activation in solid tumors.