Table 2. Mechanisms relevant to DNA biosynthesis processes in NSCLC.
| Authors | Samples | Histology [case load] | Factors | Characteristics with pemetrexed resistance |
|---|---|---|---|---|
| Bepler G et al. [2008] (38) | Tissue | SCC [19]; non-SCC [33] | TS | Upregulated |
| Christoph DC et al. [2013] (39) | Tissue | Adenocarcinoma [156]; LCC [12]; SCC [12]; others [27] | TS | Upregulated |
| Zhang D et al. [2011] (40) | PC9 & A549 cells | – | TS | Upregulated |
| Wu MF et al. [2010] (32) | A549 & H1355 cells | – | TS | Downregulated |
| Ozasa H et al. [2010] (41) | PC6 cells | – | TS copy number | Amplified |
| Shimizu T et al. [2016] (42) | Tissue | Adenocarcinoma [38]; LCC [2]; SCC [3]; others [7] | TS copy number | Amplified |
| Arévalo E et al. [2014] (44) | Tissue | Adenocarcinoma [24]; others [1] | TS 5'-UTR genotype | Without 3R/3R genotypes |
| Krawczyk P et al. [2014] (45) | Tissue | Adenocarcinoma [106]; LCC [8]; others [1] | TS 5'-UTR genotype | 3R/3R genotype with G nucleotide |
| Wang X et al. [2013] (46) | Tissue | Adenocarcinoma [119]; SCC [41] | TS 3'-UTR genotype | -6bp/+6bp genotype |
| Wu MF et al. [2010] (32) | A549 & H1355 cells | – | DHFR | Downregulated |
| Zhang D et al. [2011] (40) | PC9 & A549 cells | – | DHFR | Upregulated |
| Hanauske AR et al. [2007] (37) | Tissue | Lung cancer (unknown) | DHFR, GARFT | Upregulated |
| Bepler G et al. [2008] (38) | Tissue | SCC [19]; non-SCC [33] | RRM1 | Upregulated |
| Smit EF et al. [2009] (49) | Tissue | Adenocarcinoma [59]; LCC [24]; SCC [31]; others [7] | MTHFR genotype | SNP 677C > T: CC, CT |
| Wilson PM et al. [2012] (52) | Adenocarcinoma cells | – | dUTPase | Upregulated |
| Weeks LD et al. [2013] (53) | A549 & H1975 cells | – | UDG | Upregulated |
| Lee SH et al. [2013] (54) | Tissue | Adenocarcinoma [41] | ERCC1 | Upregulated |
| Liao WY et al. [2018] (55) | Tissue | Adenocarcinoma [58] | ERCC1 | Upregulated |
| Grabauskiene S et al. [2013] (56) | Adenocarcinoma cells | – | CHK1 | Upregulated |
| Tung CL et al. [2014] (57) | H520 & H1703 cells | – | MSH2 | Upregulated |
| Shang B et al. [2017] (58) | A549 cells | – | Ku80 | Upregulated |
SCC, squamous cell carcinoma; non-SCC, non-squamous cell carcinoma; LCC, large-cell carcinoma; TS, thymidylate synthase; UTR, untranslated region; DHFR, dihydrofolate reductase; GARFT, glycinamide ribonucleotide formyl-transferase; RRM1, ribonucleotide reductase subunit M1; MTHFR, methylenetetrahydrofolate reductase; dUTPase, deoxyuridine triphosphate nucleotidohydrolase; UDG, uracil DNA glycosylase; ERCC1, excision repair cross-complementation group 1; CHK1, checkpoint kinase 1; MSH2, human MutS homolog 2; Ku80, Ku protein subunit 80; SNP, single nucleotide polymorphism.