MYC as a therapeutic target for the treatment of triple-negative breast cancer: preclinical investigations with the novel MYC inhibitor, MYCi975
Minhong Tang 1, Shane O’Grady 1, John Crown 2, Michael J Duffy 3 4
Background: MYC is among the most often altered driver genes in triple-negative cancer of the breast (TNBC). The purpose of this research ended up being to evaluate targeting MYC to treat TNBC.
Methods: The anti-proliferative and apoptosis-inducing results of the lately discovered MYC inhibitor, MYCi975 were investigated inside a panel of 14 cancer of the breast cell lines representing the primary molecular types of cancer of the breast.
Results: IC50 values for growth inhibition by MYCi975 varied from 2.49 to 7.73 |¨¬M. Response was inversely associated with endogenous MYC levels as measured by western blotting (p = .047, r = – .5385) or ELISA (p = .001, r = – .767), i.e., reaction to MYCi975 decreased as endogenous MYC levels elevated. MYCi975 also caused variable amounts of apoptosis over the panel of cell lines, varying from no detectable induction to 80% induction. Inhibition of proliferation and induction of apoptosis were greater in TNBC compared to non-TNBC cell lines (p = .041 and p = .001, correspondingly). Finally, combined treatment with MYCi975 and only paclitaxel or doxorubicin led to enhanced cell growth inhibition.
Discussion: Our findings open the potential of targeting MYC to treat TNBC. According to our results, we recommend that trials use a mix of MYCi975 and only docetaxel or doxorubicin and can include MYC like a putative therapy predictive biomarker.