The RAS-RAF-MEK-ERK pathway regulates processes involved in the proliferation and survival of cells. KRAS mutations, prevalent in approximately 30% of patients with non-small-cell lung cancer (NSCLC), result in constitutive activation of the pathway. Selumetinib (AZD6244, ARRY-142886) is a potent and selective inhibitor of MEK1/2 which has demonstrated significant efficacy in combination with docetaxel in patients with KRAS mutant pretreated advanced NSCLC. Several trials in combination with other chemotherapy and targeted therapy regimens in lung cancer are ongoing. We review the development of selumetinib in patients with NSCLC, summarize the pharmacodynamic, pharmacokinetic and tolerability characteristics, and the available clinical trial data to understand the role of selumetinib in the treatment of NSCLC.

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The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma depends mainly on the clinical staging, as described by the new AJCC8 (American Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in patients with upper gastrointestinal cancers. We examined the prognostic significance of NLR in the era of the new AJCC8 staging system. In this single-centre cohort study, retrospective data on patients with operable GOJ adenocarcinoma treated with perioperative chemotherapy were analysed. The prognostic significance of baseline NLR in combination with AJCC8 clinical staging and other patient characteristics was examined for both time-to-progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%) underwent radical surgery. Fifty-one patients (16.2%) developed unresectable disease due to early disease progression. NLR was the only baseline factor independently associated with the development of early disease progression. AJCC8 clinical staging was significantly associated with TTP and OS. In addition, NLR ≥ 3 was predictive of poorer TTP (p = 0.001) and OS (p = 0.002), confirmed in multivariate Cox-regression analysis. NLR ≥ 3 was prognostic, especially in patients with clinical stage III for TTP (p = 0.006) and OS (p = 0.025) and in patients with clinical stage IVA for OS (p = 0.017). NLR significantly improved the prognostic classification of patients by different AJCC8 clinical stages, with a c-index improved from 0.554 to 0.592 (p < 0.001). NLR was confirmed to be an independent prognostic factor in this cohort and could be used in combination with AJCC8 clinical staging to improve the baseline prognostic stratification of patients with newly diagnosed resectable GOJ adenocarcinoma.

miRNAs are small noncoding RNA molecules that have a very important role in gene expression regulation and, therefore, in cell homeostasis. SNPs in certain miRNA-related genes have been shown to influence cancer risk and prognosis. miRNA cellular processing is complex and involves multiple proteins. XPO5 is a key factor in this process as it is responsible for the nuclear export of the precursor pre-miRNA to the cytoplasm, where it will be further processed to its final miRNA conformation in order to be loaded to RNA inducing silencing complex to exert its regulatory effect. SNPs in miRNA machinery related genes have previously been shown to influence carcinogenesis, but the role of XPO5 SNPs in its expression and function is not yet fully understood. In our review, we elaborate comprehensively on the role of XPO5 and how polymorphisms have been shown to influence cancer risk and prognosis to date.