Preclinical evaluation of novel fatty acid synthase inhibitors in primary colorectal cancer cells and a patient-derived xenograft model of colorectal cancer.

In contrast to our data from FASN knockdown cells, no significant changes were observed in the levels of 13C lactate or total lactate between control and TVB-3664 treated groups (Figure 4A ); however, we observed a similar decrease in the lactate to glucose ratio (13C-Lac /13C-Glc) in Pt 2402 and Pt 2449PT (Figure 4B ) The analysis of FASN-mediated changes in polar metabolites in tumor tissues showed a significant decrease in the pool of free adenine nucleotides (ATP + ADP + AM P = AXP) in all three PDX models analyzed; however, these changes did not reach statistical significance in the Pt 2614 model (Figure 4C ).

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