Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications

Abstract Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling—driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications—plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This moderate oxidative stress promotes tumorigenesis by inducing DNA damage, genomic instability, and aberrant activation of proliferative and survival pathways, while also contributing to resistance to conventional therapies. Paradoxically, excessive ROS accumulation can overwhelm antioxidant defenses, triggering oxidative stress-induced programmed cell death (PCD) mechanisms, including apoptosis, autophagy, and ferroptosis. Owing to its dual role—facilitating both tumor progression and suppression—ROS have emerged as compelling yet complex targets in cancer therapy. Therapeutic strategies aimed at modulating ROS homeostasis, such as enhancing ROS production, inhibiting antioxidant systems, or targeting downstream redox-regulated signaling nodes, hold promise for selectively eliminating cancer cells. Furthermore, integrating redox profiling or “redox signatures” into personalized medicine approaches may optimize therapeutic efficacy while minimizing off-target toxicity. In this review, we critically examine the Janus-faced role of ROS in carcinogenesis, dissect the molecular pathways regulated by ROS in tumor biology, and explore current advancements, limitations, and future directions in redox-based anticancer therapeutic approaches.