Myc proto-oncogene (MYC) (MYC)

The Myc proto-oncogene (MYC) is a master regulator of the human genome, encoding a transcription factor that coordinates the expression of thousands of genes involved in cell growth, proliferation, metabolism, and apoptosis (Dang CV, 2012). In healthy cells, MYC expression is tightly controlled; however, in over 70% of human cancers, the MYC gene is dysregulated through amplification, chromosomal translocation, or enhanced transcriptional activity, making it a hallmark of oncogenesis (Gabay M, et al., 2014). While the Myc protein is often described as "undruggable" due to its disordered structure, the genomic DNA of the MYC promoter contains a unique secondary structure known as a G-quadruplex (G4) in the Nuclease Hypersensitive Element (NHE) III1 region (Siddiqui-Jain A, et al., 2002). This G4 structure acts as a transcriptional "switch," and small molecules designed to stabilize it can effectively silence MYC expression at the DNA level (Brooks TA & Hurley LH, 2009). Therapeutic strategies targeting MYC genomic DNA, including G-quadruplex stabilizers and transcriptional inhibitors, represent a promising approach to treating aggressive, MYC-driven malignancies such as Burkitt lymphoma, triple-negative breast cancer, and small cell lung cancer (Xu H, et al., 2017). These agents aim to bypass the challenges of targeting the protein directly by intervening at the genetic level to reduce the overall oncogenic burden (Duff MR, et al., 2020). Clinical candidates like CX-5461 have demonstrated the potential of this approach by inducing DNA damage and inhibiting RNA polymerase I in MYC-dependent tumors (Miller MC, et al., 2021). Despite the promise, challenges remain regarding the specificity of DNA-binding agents and the potential for systemic toxicity in tissues with high regenerative capacity (Balasubramanian S, et al., 2012).

Other names

c-MycMYC proto-oncogene, bHLH transcription factorv-myc avian myelocytomatosis viral oncogene homologMRTLbHLHe39

Stabilization of G-quadruplex (G4) structures in the promoter region to inhibit transcription; inhibition of RNA polymerase I; transcriptional repression.