The impact of the Let-7 family on resistance to anticancer treatment

MiRNAs (miRNAs) represent a class of naturally occurring, small (19 to 25-nucleotides), non-coding RNA molecules. Among 16000 miRNA genes which have been identified in various species, more than 1,000 miRNAs have been reported in the humans. The lethal-7 (Let-7) gene family, which was initially found as an essential developmental gene family in Caenorhabditis elegans, is one of the most extensively studied miRNA families, and there is high evidence that these miRNAs play key roles in the initiation, growth and progression of a variety of (malignant) tumors. Based on these data, there is now a growing interest in using these molecules for clinical purposes. The present chapter therefore discusses and highlights potential diagnostic applications of members of the Let-7 family as predictors of clinical outcome and as markers for response monitoring during chemo-and/or radiotherapy. In addition, we present first promising data on the Let-7 family concerning their use as primary anticancer agents and, perhaps more importantly, as modifiers and enhancers of well-established anticancer therapy strategies. In this context, modulation of Let-7 expression seems to provide a new and very promising first-line treatment option in cancer, as well as an additive therapeutic modality to chemo-and radiotherapy, augmenting their effects and possibly reversing drug resistance-a major obstacle in modern anticancer treatment.