Integrative gas-based therapeutics for cancer treatment: Recent advances and multi-therapy innovations

Gas therapy has emerged as a promising modality for tumor treatment due to its unique advantages, including safety and efficiency, ability to enhance the drug sensitivity of cancer cells, and almost no drug resistance. In this review, we comprehensively explore the anticancer mechanisms, advantages and disadvantages of four key gas therapies: carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H₂S) and sulfur dioxide (SO₂). Recognizing the challenges of single gas therapies, we discuss their integration with advanced multi-therapy approaches, including photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT), to maximize therapeutic efficacy. Emphasis is placed on the synergistic effects of these combinations, particularly in overcoming tumor microenvironment (TME) challenges. Finally, we address the future potential of gas therapies in clinical oncology, highlighting key obstacles such as precise delivery, dose control, and translational barriers to clinical implementation.