GSE184452
Fasting Mimicking Diet blocks breast cancer and cancer stem cells escape
Metastatic tumors remain lethal due to primary/acquired resistance to therapy or cancer stem cell (CSC)-mediated repopulation. We show that a fasting-mimicking diet (FMD) activates starvation escape pathways in triple negative breast cancer (TNBC) cells, which can be identified and targeted by drugs. In CSCs, FMD cycles lower glucose-dependent protein kinase A signaling and stemness markers to reduce cell number and increase mouse survival. Accordingly, metastatic TNBC patients with lower glycemia survive longer than those with higher baseline glycemia. By contrast, in differentiated cancer cells, FMD cycles activate PI3K-AKT, mTOR and CDK4/6 as survival/growth pathways, which can be targeted by drugs to promote tumor regression. FMD cycles also prevent hyperglycemia and other toxicities caused by these drugs. These data indicate that FMD has wide and differential effects on normal, cancer and cancer stem cells, allowing the rapid identification and targeting of starvation escape pathways and providing a method potentially applicable to many malignancies. Overall design: RNA-seq of SUM159 cell line transplanted in recipient mice treated with fasting-mimicking or control diets, previously sorted for CD44 and CD24 markers to separate differentiated and cancer stem cells.