Review spotlights MYC as a multidimensional therapeutic target in cancer

A new review in Genes and Diseases explores the central role of MYC, a master regulatory protein, in the development and progression of cancer, spotlighting its potential as a multidimensional therapeutic target. MYC is dysregulated in nearly 70% of human cancers, where it influences a vast network of biological processes including cell cycle control, metabolism, apoptosis, angiogenesis, and immune evasion. The article underscores how MYC not only drives aggressive tumor behavior but also contributes significantly to drug resistance, making it one of the most compelling yet complex targets in oncology.

Historically considered undruggable due to its disordered protein structure, recent advances have begun to shift this paradigm. Researchers are now devising strategies to target MYC directly by interfering with the MYC-MAX protein complex, which activates numerous cancer-related genes. Promising compounds, such as OMO-103, have demonstrated early clinical potential by disrupting this interaction and halting tumor proliferation.

Beyond direct approaches, the review also emphasizes indirect targeting strategies, including inhibition of MYC transcription or translation, promotion of protein degradation, and synthetic lethality-wherein pathways essential to MYC-overexpressing cells are selectively disrupted. These methods aim to exploit the vulnerabilities of cancer cells that depend heavily on MYC for survival, while sparing healthy tissues.

The therapeutic potential of MYC targeting is further enhanced by innovations in small molecule inhibitors, protein degradation technologies like PROTACs, and combination therapies that integrate MYC inhibition with existing treatments. These approaches are being designed with an eye toward precision medicine, tailoring interventions based on tumor-specific MYC activity and associated molecular pathways.

However, the article cautions against oversimplification. Because MYC interacts with a wide array of partners and affects diverse signaling cascades, context-dependent effects must be carefully considered. Targeting MYC too broadly might risk unintended consequences, such as impairing normal regenerative processes or inducing premature cellular aging.

Still, with improved molecular understanding and refined drug design, the tide is turning in favor of MYC-directed interventions. This review calls attention to MYC as not just a notorious oncogene, but a gateway to novel, more effective cancer treatments-redefining what is therapeutically possible for one of the most elusive yet consequential drivers of malignancy.