RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making

Role of miRNA in distinguishing primary brain tumors from secondary tumors metastatic to the brain.

Cancer is the result of complex processes that involve multiple molecular alterations. The understanding of such complexity has been improved by the advent of a new class of small, noncoding RNA gene products known as microRNAs (or miRNAs). miRNAs play an essential role in cancer development and progression by modulating gene expression binding to target mRNA, causing either mRNA degradation or translation inhibition. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. Beyond these valuable features, miRNAs could be potentially used in the future as innovative and targeted therapeutics. Recent in vitro and expression profiling studies have identified that specific miRNAs are directly involved in brain carcinogenesis and in the metastatic process. This review focuses on metastasis-related miRNAs and on the role of miRNAs in distinguishing between primary and metastatic brain tumors. In clinical practice, miRNAs could represent a promising new class of cancer biomarkers in the diagnosis and management of brain neoplastic lesions