Is Reliance on Mitochondrial Respiration a “Chink in the Armor” of Therapy-Resistant Cancer?

A series of recent reports has suggested PGC1α-driven upregulation of mitochondrial oxidative phosphorylation as a selective vulnerability of drug-resistant cancers. Accordingly, chemical inhibitors of respiration led to selective eradication of such cancer cells due to their preferential sensitivity to mitochondrial production of reactive oxygen species. These insights create a timely opportunity for a biomarker guided application of already existing and newly emerging mitochondrial inhibitors in recurrent drug-resistant cancer, including lymphomas, melanomas, and other malignant diseases marked by increased mitochondrial respiration.