Hydrogen sulfide at the intersection of hypoxia and oxidative stress: implications for lung cancer progression and treatment – a narrative review
Year: 2026
Type: review
Abstract: Lung cancer remains a leading cause of cancer-related mortality worldwide, with a pathogenesis deeply influenced by the tumor microenvironment. Two central and interrelated factors –hypoxia and oxidative stress – contribute significantly to tumor progression, angiogenesis, metabolic reprogramming, and therapeutic resistance. In recent years, hydrogen sulfide (H 2 S), traditionally viewed as a toxic gas, has gained recognition as a critical gasotransmitter with a regulatory role in both hypoxic and redox signaling pathways in cancer biology. Endogenously produced by enzymes such as CBS, CSE, and 3-MST, H 2 S can promote or inhibit tumorigenesis depending on the context. In lung cancer, H 2 S has been shown to modulate hypoxia-inducible factor activity, support mitochondrial bioenergetics under low oxygen tension, and influence ROS dynamics, thereby maintaining redox balance that favors tumor cell survival. The complex crosstalk between H 2 S, hypoxia, and oxidative stress creates a permissive environment for tumor growth and immune evasion, but also offers potential vulnerabilities that can be therapeutically exploited. Targeting H 2 S signaling has emerged as a promising avenue in lung cancer management. Both inhibition and controlled supplementation of H 2 S are under investigation as strategies to disrupt tumor adaptation to hypoxia and oxidative stress. This review highlights the dualistic nature of H 2 S in lung cancer progression, explores its mechanisms of action in the context of hypoxic and oxidative stress pathways, and discusses the diagnostic and therapeutic potential of modulating the H 2 S axis for improved clinical outcomes.
Source: Annals of Medicine and Surgery
Authors: Emmanuel Ifeanyi Obeagu, Jomar L. Aban
Language: English
Topic: Sulfur Compounds in Biology
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,850
OpenAlex ID: W7124962903