Cancer development and therapy resistance: spotlights on the dark side of the genome.

Cancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromosome rearrangements often span areas of the genome that do not contain any known protein-coding gene. This finding is not surprising, considering that even though the vast majority of the human genome is transcribed, only a minor portion (accounting for less than 2%) encodes for proteins. Among the various classes of transcribed RNAs, long non-coding RNAs are attractive biomarkers and therapeutic targets due to their disease- and stage-restricted expression. In addition, by taking part in all the major epigenetic and post-transcriptional programs in the cell, long non-coding RNAs are emerging as key regulators of stress responses and therefore they are important non-genetic players in cancer development and progression. Here I discuss the role of lncRNAs in cancer and their promises and pitfalls as biomarkers and therapeutic targets.