Targeting MYC-driven lymphoma: lessons learned and future directions

Abstract

MYC plays a central role in tumorigenesis by orchestrating cell proliferation, growth and survival, among other transformation mechanisms. In particular, MYC has often been associated with lymphomagenesis. In fact, MYC overexpressing lymphomas such as high-grade B-cell lymphoma (HGBL) and double expressor diffuse large B-cell lymphomas (DLBCL), are considered addicted to MYC. In such a context, MYC targeting therapies are of special interest, as MYC withdrawal is expected to result in tumor regression. However, whether high MYC levels are always predictive of increased sensitivity to these approaches is not clear yet. Even though no MYC inhibitor has received regulatory approval to date, substantial efforts have been made to investigate avenues to render MYC a druggable target. Here, we summarize the different classes of molecules currently under development, which mostly target MYC indirectly in aggressive B-cell lymphomas, paying special attention to subtypes with MYC/BCL2 or BCL6 translocations or overexpression.