When fat goes down, prostate cancer is on the ropes

Figures & data

Figure 1. Therapeutic effects of FASN inhibition.

The FASN inhibitor IPI-9119 (IPI) induces a metabolic reprogramming that affects lipid synthesis and membrane composition resulting in the induction of ER stress response [i.e., Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) arm]. This is associated with global protein synthesis and more specifically AR pathway deregulation. Precision medicine approaches to select the best candidates for treatment can be based on metabolic imaging (e.g., ¹¹C-acetate) or DNA sequencing to identify genetic alterations that induce dependence on de-novo lipid synthesis. The PET/computerized tomography fused image included in the figure was kindly provided by Prof. Umar Mahmood (Massachusetts General Hospital, Boston, MA). Black arrows indicate metastatic sites. AR = androgen receptor, AR-V7 = androgen receptor, splicing variant V7, ER = endoplasmic reticulum, FASN = fatty acid synthase, mCRPC = metastatic castration-resistant prostate cancer, PET = positron emission tomography.