The MYCN protein, sometimes dubbed N-Myc, has long been studied as a target in neuronal or neuroendocrine tumors, but its role in breast cancer is less clear. It’s distinct from MYC (c-Myc), though the two are believed to affect each other.
Their intricate relationship would prove crucial in therapeutic development. But the first question is just how common they are, and according to the study, the two family members are “heterogeneously expressed in separate cell nuclei within a given tumor in at least 40% of TNBC tumors.” In fact, the expression of MYCN appeared to increase after neoadjuvant chemotherapy, part of the current standard of care.
The prevalence gave them enough reason to think about how to target it. When the team selected a cell line model, they had another finding that MYCN-expressing cells were essentially more prone to resistance to PI3K inhibitors, which block an alternative pathway for tumor growth.
Because the MYC family lack catalytic domains, the team resorted to epigenetic regulators, screening 158 compounds against the cell lines. BET drugs, which block the bromodomain (BRD)-containing family of transcriptional regulators, emerged as the winner.
It echoes an earlier study, done at Michigan State University, showing that the experimental class of molecules can prevent the growth of breast and lung cancers.
https://endpts.com/back-to-the-drawing-board-for-triple-negative-breast-cancer-targets-researchers-propose-new-combo-approach/
