From basic researches to new achievements in therapeutic strategies of KRAS-driven cancers

Among the numerous oncogenes involved in human cancers, KRAS represents the most studied and best characterized cancer-related genes. Several therapeutic strategies targeting oncogenic KRAS (KRAS(onc)) signaling pathways have been suggested, including the inhibition of synthetic lethal interactions, direct inhibition of KRAS(onc) itself, blockade of downstream KRAS(onc) effectors, prevention of post-translational KRAS(onc) modifications, inhibition of the induced stem cell-like program, targeting of metabolic peculiarities, stimulation of the immune system, inhibition of inflammation, blockade of upstream signaling pathways, targeted RNA replacement, and oncogene-induced senescence. Despite intensive and continuous efforts, KRAS(onc) remains an elusive target for cancer therapy. To highlight the progress to date, this review covers a collection of studies on therapeutic strategies for KRAS published from 1995 to date. An overview of the path of progress from earlier to more recent insights highlight novel opportunities for clinical development towards KRAS(onc)-signaling targeted therapeutics.