Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity.
While initial studies focused on the damaging effects of reactive oxygen species, a recent paradigm shift has shown
that mROS can act as signaling molecules to activate pro-growth responses. Cancer cells have long been observed
to have increased production of ROS relative to normal cells, although the implications of this increase were not
always clear. This is especially interesting considering cancer cells often also induce expression of antioxidant
proteins. Here, we discuss how cancer-associated mutations and microenvironments can increase production of
mROS, which can lead to activation of tumorigenic signaling and metabolic reprogramming. This tumorigenic
signaling also increases expression of antioxidant proteins to balance the high production of ROS to maintain
redox homeostasis. We also discuss how cancer-specific modifications to ROS and antioxidants may be targeted
for therapy.