BRCA1 involves in homologous recombination, nonhomologous end joi

BRCA1 involves in homologous recombination, nonhomologous end joining, mismatch repair and other effects though its interaction with other DNA repair gene such as ATM, ATR, RAD51, RAD50, MRE11, NBS1. BRCA2 and so on [7]. The reason that high/positive BRCA1 could predict the good response to taxol is still not clear, 3 mechanisms find more had been proposed

in explained this issue: (1) trigger cell cycle arrest in G2/M phase, (2) enhance apoptosis through a pathway involving H-Ras, MEKK4, JNK, and activation of caspases 8 and 9, (3) participate in spindle assembly checkpoint signaling [6, 40]. BRCA1 gene showed an interesting outcome in NSCLC chemotherapy. Several cell studies and our meta-analysis based on clinical trials demonstrated low/negative BRCA1 expression could benefit from platinum-based chemotherapy; in contrast, the high level of BRCA1 expression was in favor of toxal contained agents. This may confuse us, how could we determine chemotherapy choice properly? Rosell customized treated 84 patients based on their BRCA1 expression: low, cisplatin plus gemcitabine (GP); Eltanexor in vivo intermediate, cisplatin plus docetaxel (DC);

high, docetaxel alone. The median survival (MS) and 2-year survival of low BRCA1 patients received GP regime was 11 month and 41.2%, which seem to be favorable with the traditional randomized trial treated with GP or pemetrexed plus cisplatin. The MS of high BRCA1 patients received single-agent Ergoloid docetaxel was 11 month and had no detrimental effect when compared with a large phase III trial in patients treated with DC [41]. If this hypothesis is validated, the NSCLC patients with high BRCA1 should receive taxol based and non-platinum-contained adjuvant chemotherapy, which would be more economic, efficacy and less toxic effect for patients. However, more multi-center prospective clinical trials should be conducted to confirm this hypothesis. Since BRCA1 mRNA and protein level was associated with treatment efficacy, why other biomarkers such as SNPs in this gene

could be a choice? But in another hand, it seems that gene expression level provides direct evidence and SNPs small molecule library screening provide indirect evidence as it is usually gene product especially protein rather than gene itself play an import role in biochemical activity. Although SNPs are important gene variant that affect the protein expression, but many factors involve in protein synthesis. We found that studies evaluated the SNPs in BRCA1 gene and the clinical outcome was limited. Su [42] found that BRCA1 S1613G was associated with platinum-based chemotherapy efficacy in objective response rate. In a large trail consisted of 300 NSCLC patients at stages III and IV, AACC haplotype but not single S1613G in BRCA1 was associated with poor overall survival (hazard ratio = 2.097; 95%CI, 1.339 to 3.284) treated with platinum combination chemotherapy [43].

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