Fig. 2.

Cryo-EM technology as an important tool for precision oncology. a The new cyro-EM technology could provide a better understanding of the native/physiological state of protein complexes for the development of promising therapeutic targets and drug discovery for precision oncology. Reprinted from publication: Merk, A. et al., Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery, 1698-707, 2016, with permission from Elsevier.¹²⁶ b Mitochondrial inhibitors, like metformin, enasidenib or etomoxir, have been used to treat cancer patients. An ideal scenario to exploit the resistance mechanism in cancer cells that seems to rely on OxPhos activity could be achieved using the concept of metabolic vulnerability, when a combination of targetable genes leads to a lethal phenotype. The PGC-1/ERR axis has great potential to be included as a potential metabolic target for precision oncology for the treatment of non-responder patients. Thus, the combination of mitochondrial inhibitors and inverse agonists of the PGC-1/ERR axis, like compound 29, might provide new hope for treating non-responder patients whose cancer cell survival mechanism relies on mitochondrial metabolism