Abstract
The Ras-Related signaling pathway plays an important role in cell development and differentiation. A growing body of evidence collected in recent years has shown that the aberrant activation of Ras is associated with tumor-related processes. Several studies have indicated that indole and its derivatives can target regulatory factors and interfere with or even block the aberrant Ras-Related pathway to treat or improve malignant tumors. In this review, we summarize the roles of indole and its derivatives in the isoprenylcysteine carboxyl methyltransferase-participant Ras membrane localization signaling pathway and Ras-GTP/Raf/MAPK signaling pathway through their regulatory mechanisms. Moreover, we briefly discuss the current treatment strategies that target these pathways. Our review will help guide the further study of the application of Ras-Related signaling pathway inhibitors.
Highlights
Cancer poses a great threat to human health, and numerous oncogenes have been identified
Significant progress has been achieved in the discovery of Ras-Related signaling pathway inhibitors containing indole skeletons as new potential antitumor drugs
Indole derivatives can participate in this mechanism in two ways to inhibit Ras action: by directly interfering with SOS proteins and through the negative feedback regulation of SOS proteins
Summary
Cancer poses a great threat to human health, and numerous oncogenes have been identified. One of the most common proto-oncogenes in human cancer, plays an important role in tumor development. About 30% of human malignancies are associated with Ras mutations (Hunter et al, 2015). Superfamily Ras proteins exist in two states: the GTP-bound “on” state and GDP-bound “off ” state. Mutated Ras proteins initiate cell transformation, drive mutant oncogenesis, and promote tumor maintenance. Several new breakthroughs have been made in research on the direct targeting of Ras proteins (Figure 1; Taveras et al, 1997; Karaquni et al, 2002a,b; Ostrem et al, 2013; Shima et al, 2013; Lim et al, 2014; Patricelli et al, 2016).
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