Mitochondrial enzyme found to block cell death pathway points to new cancer treatment strategy

The Scientific Committee of the World Mitochondria Society would like to share this article by Chao Mao and al. on Mitochondrial enzyme found to block cell death pathway points to new cancer treatment strategy.

Credit: CC0 Public Domain

The Scope is: The mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) plays an important and previously unknown role in blocking a form of cell death called ferroptosis, according to a new study by researchers at The University of Texas MD Anderson Cancer Center. Preclinical findings suggest that targeting DHODH can restore ferroptosis-driven cell death, pointing to new therapeutic strategies that may be used to induce ferroptosis and inhibit tumor growth.

To conclude: In GPX4-low cancers, brequinar effectively induced ferroptosis and suppressed tumor growth, but the effects were not seen in GPX4-high cancers. However, the combination of brequinar and sulfasalazine, an FDA-approved ferroptosis inducer, resulted in a synergistic effect to overcome high GPX4 expression and to block tumor growth.

DOI: 10.1038/s41586-021-03539-7