Anti-c-myc RNAi-Based Onconanotherapeutics

Abstract

Overexpression of the c-myc proto-oncogene features prominently in most human cancers. Early studies established that inhibiting the expression of oncogenic c-myc, produced potent anti-cancer effects. This gave rise to the notion that an appropriate c-myc silencing agent might provide a broadly applicable and more effective form of cancer treatment than is currently available. The endogenous mechanism of RNA interference (RNAi), through which small RNA molecules induce gene silencing by binding to complementary mRNA transcripts, represents an attractive avenue for c-myc inhibition. However, the development of a clinically viable, anti-c-myc RNAi-based platform is largely dependent upon the design of an appropriate carrier of the effector nucleic acids. To date, organic and inorganic nanoparticles were assessed both in vitro and in vivo, as carriers of small interfering RNA (siRNA), DICER-substrate siRNA (DsiRNA), and short hairpin RNA (shRNA) expression plasmids, directed against the c-myc oncogene. We review here the various anti-c-myc RNAi-based nanosystems that have come to the fore, especially between 2005 and 2020.

The long journey to bring a Myc inhibitor to the clinic

“…Unfortunately, the trial did not meet expectations of Myc knockdown or efficacy and was discontinued. For a recent review on the subject, please refer to Habib et al (2020) .…”

Lipid Nanoparticles: Promising Treatment Approach for Parkinson’s Disease

“…Liposomes were initially identified in the 1960s following the spontaneous formation of closed lipid bilayers in water [ 52 ]. It remains a popular choice for lipid-based vehicles because of its simple structure [ 53 ]. These NPs are composed of an aqueous core that encapsulates the drug or gene of choice and is enclosed in a unilamellar or multilamellar phospholipid bilayer that contains both hydrophilic and hydrophobic groups ( Figure 3 ) [ 54 ].…”

USP13: Multiple Functions and Target Inhibition

“…The c-Myc gene encodes a proto-oncoprotein, a widely recognized transcription factor regulating approximately 10–15% of genes implicated in cell proliferation, differentiation, apoptosis and other processes ( Friedman et al, 2017 ; Habib et al, 2020 ), and c-Myc mutations are often associated with tumors ( Berns et al, 1997 ; Brodsky and McCracken, 1999 ; Hermeking et al, 2000 ; Morrish et al, 2003 ; Wilson et al, 2004 ). Recently, it has been reported that USP13 is co-overexpressed with c-Myc in many tumors, such as NSCLC ( Wu et al, 2019 ), cholangiocarcinoma (CAA) ( Zhou et al, 2020 ), GSCs ( Fang et al, 2017 ), and hepatocellular carcinoma (HCC) ( Huang et al, 2020 ).…”