Zeta RRM1 Antibody. Zeta’s rabbit recombinant antibody recognizes RRM1 (Ribonucleotide Reductase M1 polypeptide), which is involved in carcinogenesis, tumor progression, and the response of non-small-cell lung cancer (NSCLC) to chemotherapy.
RRM1 is one of two non-identical subunits for ribonucleoside-diphosphate reductase, an enzyme that catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. RRM1 provides the precursors necessary for DNA synthesis. RRM1 is present throughout the cell division cycle but downregulated in quiescent cells. RRM1 and RRM2 subunites come together to form RNR (Ribonucleotide Reductase), which catalyzes the rate-limiting step of de novo synthesis of deoxyribonucleotide triphosphates (dNTPs) building blocks for DNA synthesis, and is a well-recognized target for cancer therapy.
RNR is a heterotetramer consisting of two large RRM1 subunits and two small RRM2 subunits. RNR activity is greatly stimulated by transcriptional activation of RRM2 during S/G2 phase to ensure adequate dNTP supply for DNA replication. RRM1 is phosphorylated at Ser 559 by CDK2/cyclin A during S/G2 phase. And this S559 phosphorylation of RRM1enhances RNR enzymatic activity and is required for maintaining sufficient dNTPs during normal DNA replication (Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition | Oncogene (nature.com)). Defective RRM1 phosphorylation causes DNA replication stress, double-strand break, and genomic instability. Combined targeting of RRM1 phosphorylation and ATR triggers lethal replication stress and profound antitumor effects. Thus, this posttranslational phosphorylation of RRM1 provides an alternative mechanism to finely regulating RNR and therapeutic opportunities for cancer treatment.
RRM1 has emerged as a promising biomarker to predict the efficacy of gemcitabine where studies have show that tailored chemotherapy based on RRM1 immunohistochemical (IHC) expression provides a benefit for patients with advanced non-small cell lung cancer (NSCLC). RRM1- expression in advanced NSCLC is associated with a higher response rate to gemcitabine-based chemotherapy. In patients with RRM1+ tumors, docetaxel and vinorelbine showed a higher therapeutic efficacy than gemcitabine-based therapy (Response to first-line chemotherapy in patients with non-small cell lung cancer according to RRM1 expression – PubMed (nih.gov)).