Excision repair cross-complementary group for chemotherapy efficacy in gastric cancer

Excision repair cross-complementary group 1 (ERCC1) is a significant protein in the nucleotide excision repair pathway. ERCC1 activity has been previously reported as a significant biomarker for the efficacy of platinum-based chemotherapy in some cancers such as lung, ovary, gastric and colorectal cancer. In gastric cancer, the results of previous studies on mRNA/immunohistochemical (IHC)/polymorphism of ERCC1 in patients who received platinum-based chemotherapy varied among different studies. The large-scale translational analyses of JCOG 9912 trial revealed that a high level of ERCC1 is considered a poor prognostic factor in terms of overall survival (OS) in advanced gastric cancer patients who received systemic chemotherapy. The ERCC1 mRNA expression in the diffuse type adenocarcinoma was significantly higher than the expression in the intestinal type. For these patients with poor prognosis such as high ERCC1 value and diffuse type adenocarcinoma, a triplet regimen as first-line chemotherapy was considered to be more active than a doublet regimen. JCOG 1013 is a randomized phase III trial that investigates the superiority of a triplet regimen of docetaxel, S-1 and cisplatin in relation to S-1 and cisplatin in patients with unresectable or recurrent gastric cancer. This study also investigates differences in OS according to tumor tissue classification (intestinal type vs. diffuse type) as a key secondary endpoint. As a future approach, strict guidelines for standard protocols regarding sample collection and preservation of samples are required and we may need to develop the target-specific antibodies for functional ERCC1 isoforms. These improvements would solve the methodological heterogeneity of ERCC1 determinations and large-scale randomized trials to validate the roles of molecular markers, including ERCC1 expression, in advanced gastric cancer patients who receive platinum-based chemotherapy are required in the future.