The present invention relates to methods for treatment of tumors comprising administering to a subject in need thereof a DNA damaging agent and a ribonucleotide reductase inhibitor. The ribonucleotide reductase inhibitor can sensitize tumor cells to the DNA damaging agent, thus permitting greater treatment efficacy than the DNA damaging agent alone. The methods described herein are generally useful for treating any tumor that can benefit from this combination therapy. In particular, the methods described herein are useful for treating tumors that are resistant or have the propensity to develop resistance to certain DNA damaging agents. Further provided in the prevent invention are compositions comprising a DNA damaging agent and a ribonucleotide reductase inhibitor.