A major challenge in cancer treatment is the presence of cancer stem cells (CSC), which play a significant role in therapeutic resistance, metastatic progression, and tumor relapse, highlighting their importance as therapeutic targets. Photodynamic therapy (PDT) can be a valuable strategy for targeting CSC by increasing reactive oxygen species via light-activated photosensitizers, thereby counteracting CSC features of resistance. Therefore, this manuscript reviews the existing evidence on PDT-based approaches targeted at CSC. The literature search was conducted using the Medline (through PubMed), Web of Science, and Embase databases. The inclusion criteria were in vitro, in vivo, and clinical studies addressing PDT-based therapeutic strategies targeting CSC. A total of 37 publications were included in this review. From this analysis, we identified several studies with CSC-associated targets, delivery of PDT systems to CSC, novel nanoplatforms that disrupted the CSC microenvironment, and combined strategies to enhance PDT efficacy. The existing strategies have shown success in reducing CSC populations across different cancers by decreasing viability and tumor growth, as well as limiting stemness properties. However, some technical and biological constraints can limit translation, and, to the best of our knowledge, no clinical studies have been reported.
Serambeque et al. (2026) studied this question.