Combination of BRAF inhibitor and MEK inhibitor is current Standard of Care (SoC) for BRAF-mutated melanoma. However, almost all patients develop resistance to these agents and one of the resistance mechanisms is BRAF overexpression. To overcome this kind of resistance, Takano and colleagues discovered novel ATP-competitive MEK inhibitors, DS56771486 and DS03090629. These compounds tended to retain their activities in BRAF overexpressed A375 cell line whereas currently used BRAF inhibitor and MEK inhibitor got attenuated in this cell line compared to parental A375. These results indicate the potential of these compounds to overcome the resistance to current SoC in BRAF-mutated melanoma.
PARP inhibitors are widely available to patients with homologous recombination deficient breast, ovarian, pancreatic, or prostate cancers. The use of current PARP inhibitors as chemo-potentiating agents have been limited due to toxicities. Lee and colleagues developed a next generation PARP inhibitor venadaparib. Molecular characteristics of venadaparib translated to superior efficacy...
