Rac1 repression reverses chemoresistance by targeting tumor metabolism

Abstract

Tumor metabolism is exemplified by the increased rate of glucose utilization, a biochemical signature of cancer cells. The enhanced glucose hydrolysis enabled by the augmentation of glycolytic flux and the pentose phosphate pathway (PPP) plays a pivotal role in the growth and survival of neoplastic cells. In a recent report, it has been shown that in human breast cancer the GTP binding protein, Rac1 enables resistance to therapy, particularly against the DNA-damaging therapeutics. Significantly, the findings demonstrate that Rac1-dependent chemoresistance involves the upregulation of glycolytic flux as well as PPP. Using multiple approaches, the study demonstrates that disruption of Rac1 activity sensitizes cancer cells to DNA-damaging agents. More importantly, the data uncover a previously unknown PPP regulatory role of Rac1 in breast cancer. Finally, the authors also show the effectiveness and the feasibility of in vivo targeting of Rac1 to enhance the chemosensitivity of breast cancer. This elegant report provokes scientific curiosity to expand our understanding of the intricacies of the role and regulation of Rac1 in cancer.