Figure 2.

The mechanisms by which MYC induces apoptosis. The P53-dependent pathway to MYC-induced death is primarily mediated by the ARF-MDM-P53 axis following the upregulation of ARF expression by MYC. This leads to the stabilisation of P53 and the induction of P53 pro-apoptotic target genes. In contrast, the P53-independent pathway to MYC-induced apoptosis is reliant on the direct transcription of pro-apoptotic genes or the repression of pro-survival protein expression. Given the cooperativity between MYC signalling and the BCL-2-regulated apoptotic pathway in promoting tumourigenesis, combining drugs targeting both arms (e.g., MYC with JQ1, BCL-2 pro-survival proteins with BH3-mimetics) is a promising therapeutic avenue (see Section 5). Figure created with Biorender.com.