PPARGC1A and cancer: This aligns with the emerging role of PGC-1α in driving bioenergetic flexibility and metabolic plasticity in the face of survival challenges involved in cancer progression (Tan et al., 2016; McGuirk et al., 2020; Andrzejewski et al., 2017); advanced cancers need to be adaptable, and thereby the context-dependent adaptations conferred by PGC-1α could further contribute to the difficulty in treating advanced cancers.