MicroRNA-Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer

摘要: MicroRNAs (miRs) have been causally implicated in the progression and development of a wide variety cancers. miRs modulate activity key cell signaling networks by regulating translation pathway component proteins. Thus, pharmacological targeting that regulate cancer networks, either promoting (using miR-supplementation) or suppressing antisense oligonucleotide-based strategies) miR is an area intense research. The RAS-extracellular signal regulated kinase (ERK) represents major miR-regulated network endows cells with some classical hallmarks cancer, often inappropriately activated malignancies somatic genetic alteration through point mutation gene copy number. In addition, recent progress indicates many tumors may be deficient GTPase activating proteins (GAPs) due to collaborative action oncogenic miRs. Recent studies also suggest harboring mutant RAS allele there critical role for wild type determining overall RAS-ERK activity. Together, these two advances comprise new opportunity therapeutic intervention. this review, we evaluate miR-based strategies modulating cancers; particular more direct modulation RAS-GTP levels, potential complement current yield durable treatment responses. To end, discuss therapies focused on three prominent including pan-RAS regulator let-7 GAP comprised miR-206 miR-21 (miR-206/21).