Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth.

ABSTRACT: Kidney cancer (or renal cell carcinoma, RCC) is the sixth most common malignancy in the United States and one of the relatively few whose incidence is increasing. Because of the near universal resistance which occurs with the use of current treatment regimens, reprogrammed metabolic pathways are being investigated as potential targets for novel therapies of this disease. Borrowing from studies on other malignancies, we have identified the PAK4 and NAD biosynthetic pathways as being essential for RCC growth. We now show, using the dual PAK4/NAMPT inhibitor KPT-9274, that interference with these signaling pathways results in reduction of G2-M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. Mechanistic studies demonstrate

SUBMITTER: Abu Aboud O 

PROVIDER: S-EPMC5010932 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature