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Chapter 116esophageal cancer (41, 42). Systemic treatment options for patients with advanced esophageal and gastric cancer are further described in detail in the summarizing discussion of this thesis. In chapter 4 we describe the results of a multicenter randomized open label phase 2 trial aiming to improve the RR of palliative first-line chemotherapy for patients with advanced EC and GC by adding folic acid and vitamin B12 to the at the time commonly used schedule of cisplatin in combination with gemcitabine (43, 44). The rationale for adding folic acid and vitamin B12 was based on the efficacy and toxicity benefits that were observed in a phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant mesothelioma(45). Preclinical evidence demonstrated that differences in the folate environment resulted in a different sensitivity of human cancer cell lines to cisplatin (46, 47).In chapter 4, we first investigated the sensitivity of adenocarcinoma cell lines for cisplatin under high and low folate conditions. The observation that adenocarcinoma cells grown under high folate conditions appeared to be more sensitive to the effects of cisplatin and the intracellular platinum accumulation was higher in these cells, provided further preclinical support for the clinical study evaluating the addition of folic acid and vitamin B12 suppletion to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer as described in chapter 4.In the current landscape of increased treatment options and increasing medicine costs, patient selection for the right treatment is very important to avoid unnecessary exposure of patients to toxic treatments and to enhance efficient use of financial resources. Predictive and prognostic biomarkers are important to select patients that may benefit most from treatment (48). MicroRNAs (miRNAs) are extensively studied as potential biomarkers for different tumor types. miRNAs are endogenous, evolutionarily conserved, small non-coding RNAs, that regulate post-transcriptional gene expression through complementary binding to the 3'untranslated regions (3'UTRs) of target messenger RNA (mRNA) genes (49). A landmark study in 2005 demonstrated that tissue miRNA expression profiles have the ability to classify different types of human cancer, highlighting the potential of miRNA profiling as tool for cancer diagnosis (50). It appeared that miRNAs that target tumor suppressor genes function as oncogenes while miRNAs that target oncogenes exert a tumor suppressor function in different cancer types (51). This is further explained in figure 2.