Source: Medical Gas Research

Published: 2026 May

PubMed ID: 42157432

DOI: 10.4103/mgr.MEDGASRES-D-25-00315

Photodynamic therapy is a noninvasive anticancer treatment that uses light-activated photosensitizers to generate reactive oxygen species. However, its clinical efficacy is severely limited by tumor hypoxia and rapid oxygen depletion during the type II photochemical reaction. To address these challenges, we synthesized data from randomized controlled trials and meta-analyses published between 2000 and 2025. Our review shows that photodynamic therapy significantly increases survival rates in patients with malignant pleural effusion and achieves high complete response rates in patients with esophageal and gastric cancers. However, a risk-of-bias assessment reveals limitations in study design regarding blinding and sample size. Crucially, we identify gas-mediated therapies as the next paradigm shift. This review discusses emerging strategies to overcome tumor hypoxia and improve the efficacy of photodynamic therapy. These strategies include oxygen-generating nanoplatforms, tumor microenvironment modulation, and combination approaches with chemotherapy, radiotherapy, and immunotherapy. Additionally, we discuss the critical role of sequential immunotherapy and propose standardized dosimetry protocols that report irradiance and drug-light intervals. These protocols aim to facilitate global regulatory harmonization and clinical reproducibility.