Nevertheless, a comparison of surgical outcomes between patients treated at the Memorial Sloan Kettering Cancer Center, where D2 resection is extensively carried out, and patients treated in Korea revealed

better disease-specific survival for the latter group [23]. Therefore, it is foreseeable that underlying biological differences play a crucial role, and growing evidence indicate that the molecular taxonomy of gastric cancer is influenced by ethnic factors. MicroRNA expression profiling, which is emerging as an excellent classifier in oncology, and next-generation sequencing studies are beginning to unveil the existence of different sets of deregulated gene networks potentially correlated CBL0137 with ethnicity [24–26]. Furthermore, the molecular analysis of the ToGA trial revealed that HER2 positivity is associated with the intestinal-type gastric cancer (32.5% intestinal vs 6.0% diffuse), the most common histology in Asia [8]. Overall, the different ethnicity-related

molecular landscape of gastric cancer might XAV-939 manufacturer Kinase Inhibitor Library ic50 reflect a different expression of therapeutic targets and, in turn, sensitivity to anticancer agents. Beyond tumor biology, also pharmacogenomic differences should be taken into account. For instance, while S1 is extensively used in front-line in Asia, its use in the Western hemisphere was initially constrained by evidence of more severe toxicity in Caucasian patients [27]. The different magnitude of toxic effects is thought to be correlated with CYP2A6 gene polymorphisms, affecting the conversion of S1 to fluorouracil. Indeed, in the phase III FLAG study conducted in non-Asian countries S1 was used at a lower dose compared to Japanese studies [28], despite the higher body surface of Western patients. Next, in the European FFCD-GERCOR-FNCLCC trial 416 patients were randomized

to receive two different sequential strategies in first- and second-line: epirubicin, cisplatin and capecitabine in first-line and FOLFIRI in second-line vs the reverse sequence Urease [29]. The sequence with FOLFIRI in first-line resulted superior for the primary endpoint (time to treatment failure), a benefit deriving from the better tolerance and the correlated lower rate of treatment discontinuation. However, no firm conclusions can be drawn from this trial having been only presented in abstract form to date. Finally, a recent retrospective Turkish study reported data from 97 docetaxel-pretreated patients who received FOLFIRI in the second-line setting [30]. Investigators reported an ORR of 26.8% and a DCR of 58.8%. However, it is worth considering that 19 patients (19.5%) had locally recurrent gastric cancer and 47 patients (48.5%) had only one metastatic site.