In conclusion, pre-treatment serum HBsAg/HBV DNA ratio can predict long-term VR to entecavir therapy in nucleos(t)ide-na?ve CHB patients. Abbreviations ALT thoroughly alanine aminotransferase AUC area under the curve CHB chronic hepatitis B HBV hepatitis B virus NA nucleos(t)ide analog peg-IFN pegylated interferon ROC receiver operating characteristic curve VR virologic response
Gastric cancer is the second most common cause of cancer-related death worldwide (1). Gastric adenocarcinoma has a poor outcome since high percentage of cases present with advanced disease. Chemotherapy has been considered to be useful treatment for advanced gastric cancer, but its current 5-year survival rate is less than 20% (1,2). Accordingly, the unmet need of effective treatment has led to an intensive effort to examine molecular regulators.

Furthermore, based on the previous research that gastric cancer results from accumulated genetic alterations, which affect essential cellular functions for tumorigenesis, investigations to find a good predictive biomarker for targeted therapy have been undertaken in recent years in order to improve present therapeutics (1,3). The PI3K/AKT pathway is known to play a key role in regulating various cellular processes, such as proliferation, growth, apoptosis, cytoskeletal rearrangement and cell metabolism (4,5). In gastric cancer, the PI3K/AKT signaling is inappropriately activated through mutation or alteration of many components of the PI3K pathway.

Up to now, the mechanisms observed widely for PI3K/AKT activation in gastric cancer include somatic activating mutations and amplifications in p110�� (6�C8), loss of the PTEN tumor suppressor (8), and genetic amplifications of AKT1 (9). Preclinical study of human gastric cancer cell lines has demonstrated the anti-proliferative effect of PI3K inhibition by LY294002 or mTOR inhibition by everolimus and evidenced the synergistic efficacy with 5-fluorouracil or sunitinib, indicating a role for the PI3K/AKT pathway in gastric cancer carcinogenesis (10�C12). In addition to gastric adenocarcinoma, the PI3K/AKT pathway has been an attractive target in clinical studies of various human cancers. Agents targeting PI3K/AKT pathway in clinical development are pure PI3K inhibitors including NVP-BKM120, dual PI3K-mTOR inhibitors, AKT inhibitors and mTOR inhibitors. Isoform-specific PI3K inhibitors are also emerging. According to previous studies, specific genetic alterations, such as HER2 amplification and PIK3CA mutation, were revealed as biomarkers for sensitivity to the PI3K inhibitor in breast cancer (13). However, cancers harboring KRAS mutations are likely to be insensitive to single-agent PI3K inhibitors and showed synergism Drug_discovery in combination treatment with MEK inhibitors (14,15).