Recent Advances of mTOR Inhibitors Use in Autosomal Dominant Polycystic Kidney Disease: Is the Road Still Open?

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most common monogenic kidney disease, is caused by mutations in the PKD1, PKD2 or, in a very limited number of families, GANAB genes. Although cellular and molecular mechanisms of this disease have been understood in the past 20 years, specific therapy approaches remain very little. Both experimental and clinical studies show that the mammalian or mechanistic target of rapamycin (mTOR) pathway plays an important role during cyst formation and enlargement in ADPKD. Studies in rodent models of ADPKD showed that mTOR inhibitors had a significant and long-lasting decrease in kidney volume and amelioration in kidney function. In the past over ten years, researchers have been devoting continuously to test mTOR inhibitors efficacy and safety in both preclinical studies and clinical trials in patients with ADPKD. In this review, we will discuss the mTOR pathway thoroughly, mainly focusing on current advances in understanding its role in ADPKD, especially the recent progress of mTOR inhibitors use in preclinical studies and clinical trials.