Abstract
The MYC gene which consists of 3 paralogs, C-MYC, N-MYC and L-MYC, is one of the most frequently deregulated driver genes in human cancer. Because of its high prevalence of deregulation and its causal role in cancer formation, maintenance and progression, targeting MYC is theoretically an attractive strategy for treating cancer. As a potential anticancer target, MYC was traditionally regarded as undruggable due to the absence of a suitable pocket for high-affinity binding by low molecular weight inhibitors. In recent years however, several compounds that directly or indirectly inhibit MYC have been shown to have anticancer activity in preclinical tumor models. Amongst the most detailed investigated strategies for targeting MYC are inhibition of its binding to its obligate interaction partner MAX, prevention of MYC expression and blocking of genes exhibiting synthetic lethality with overexpression of MYC. One of the most extensively investigated MYC inhibitors is a peptide/mini-protein known as OmoMYC. OmoMYC, which acts by blocking the binding of all 3 forms of MYC to their target promoters, has been shown to exhibit anticancer activity in a diverse range of preclinical models, with minimal side effects. Based on its broad efficacy and limited toxicity, OmoMYC is currently being developed for evaluation in clinical trials. Although no compound directly targeting MYC has yet progressed to clinical testing, APTO-253, which partly acts by decreasing expression of MYC, is currently undergoing a phase I clinical trial in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
Highlights
MYC is one of the most widely investigated cancer-causing genes, being implicated in the formation, maintenance and progression of several different cancer types [1,2,3]
The MYC gene family consists of 3 members, C-MYC, L-MYC and N-MYC, all of which belong to the su perfamily of basic helix-loop-helix leucine zipper DNA bind ing proteins [1,2,3]
MYC proteins largely function as transcriptional modulators, regulating genes involved in several different cellular pro cesses including cell growth, cell cycle, differentiation, apoptosis, angiogenesis, metabolism, DNA repair, protein translation, immune response and stem cell formation [1,2,3,4]
Summary
MYC is one of the most widely investigated cancer-causing genes, being implicated in the formation, maintenance and progression of several different cancer types [1,2,3]. Following MYC-MAX interaction, the dimeric complex preferentially binds to DNA response elements, known as enhancers or E-boxes con taining the consensus DNA sequence, CACGTG (or related sequences) [30,31] These sequences are abundant across the genome, they are enriched at promoter sites of genes involved in regulating cell proliferation. Mechanisms giving rise to these alterations include gene amplification, chromosomal translocation, retroviral promoter insertion, activation of super enhancers, enhanced cell signalling, altered protein degradation and mutation (Table 1) [38,39,40,41,42,43] Of these mechanisms, gene amplification appears to be one of the most frequent mechanisms for MYC activation in solid human cancers. N-MYC can be amplified or overexpressed in tumors with neuroendocrine features such as neuroblastoma, retinoblastoma, medullablastoma, small-cell lung cancer and prostate cancer (neuroendocrine type) [45], while L-MYC was reported to be amplified in a small number of small-cell lung cancers [46]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
