Differential Effect of Polymorphisms of CMPK1 and RRM1 on Survival in Advanced Non-small Cell Lung Cancer Patients Treated with Gemcitabine or Taxane/Cisplatinum

Abstract

These findings suggest that polymorphisms of CMPK1 and their combination with those of RRM1 are helpful in identifying patients who will benefit less from a gemcitabine/cisplatinum as the first-line regimen.

Pathway-Based Pharmacogenomics of Gemcitabine Pharmacokinetics in Patients with Solid Tumors

“…This SNP occurs in LD with 14 other SNPs on CMPK locus as shown in Table 2. Although functional characterization of these SNPs has not yet been carried out, recently one of the SNPs in this LD group, rs449266 has been shown to be associated with survival in NSCLC patients [19]. Functional characterization of CMPK SNPs is required to further understand the underlying molecular mechanism of the observed association.…”

The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient

“…In the available literature six studies describe the relationship between SNPs of RRM1 and the duration of the PFS (Dong et al, Mlak et al, Vinolas et al, Isla et al, Kim et al, Ludovini et al) and OS (Ryu et al, Mlak et al, Vinolas et al, Isla et al, Kim et al, Ludovini et al) in patients with NSCLC treated in the first-line with platinum and third generation drug scheme (usually gemcitabine) [16, 20, 22–26]. Dong et al presented the positive study regarding the impact of RRM1 SNPs on the length of PFS.…”

PharmGKB summary

“…The CC genotype rs1044457(C>T), a 3’UTR SNP, is associated with decreased formation of dFdCTP in patients with a variety of solid tumors [34], and a study of pancreatic cancer patients reports that the CC genotype is associated with improved overall survival, and a longer time to tumor and disease progression [20]. A third study in lung cancer patients reports no association between the CC genotype in rs1044457 and patient response [46]. …”