Combination therapy of RRM2 siRNA and endocrine therapy or chemotherapy for treatment of Luminal A breast cancer

Abstract

Ribonucleotide reductase M2 (RRM2) subunit is one of two subunits that constitute ribonucleotide reductase, the enzyme that converts ribonucleotide 5'-diphosphates into 2'-deoxyribonucleotides, which are required for DNA synthesis. The overexpression of RRM2 was associated with tumor aggression and higher risk of relapse in even Luminal A– the least aggressive breast cancer subtype. In this study, the therapeutic potential of targeting RRM2 was investigated in Luminal A subtype. Suppression of ribonucleotide reductase M2 subunit synthesis, using small interfering RNA, inhibited cell growth, clonogenicity, wound healing ability and triggered G1 phase cell cycle arrest in Luminal A breast cancer cell lines. Targeting RRM2 as a therapy was demonstrated to show synergistic effect with Tamoxifen and Doxorubicin in the inhibition of MCF-7 cell line. The study suggests that suppression of RRM2 (and its function) is a potential therapeutic strategy and combined therapy of targeting RRM2 and endocrine or chemotherapy is recommended for poor prognosis Luminal A patients whose RRM2 expression is elevated.