Inhibiting RRM2 to enhance the anticancer activity of chemotherapy

[Display omitted] •RRM2 can be used as a biomarker of chemotherapy response and prognosis.•RRM2 is upregulated by gene, transcriptional and post-transcriptional levels.•Overexpression of RRM2 facilitates DNA damage repair and affects signaling pathway.•SiRNA, RRM2 inhibitors and kinase inhibitors suppress RRM2 expression or activity. RRM2, the small subunit of ribonucleotide reductase, is identified as a tumor promotor and therapeutic target. It is common to see the overexpression of RRM2 in chemo-resistant cancer cells and patients. RRM2 mediates the resistance of many chemotherapeutic drugs and could become the predictor for chemosensitivity and prognosis. Therefore, inhibition of RRM2 may be an effective means to enhance the anticancer activity of chemotherapy. This review tries to discuss the mechanisms of RRM2 overexpression and the role of RRM2 in resistance to chemotherapy. Additionally, we compile the studies on small interfering RNA targets RRM2, RRM2 inhibitors, kinase inhibitors, and other ways that could overcome the resistance of chemotherapy or exert synergistic anticancer activity with chemotherapy through the expression inhibition or the enzyme inactivation of RRM2.