Overcoming photodynamic therapy resistance via DNA repair inhibitors: Advanced review

Photodynamic therapy (PDT) is an innovative treatment modality used in cancer therapy and non-malignant diseases. Despite significant advancements in PDT administration, resistance in certain tumors typically limits an increase in survival rates. One strategy to improve PDT outcomes is using DNA repair inhibitors to disrupt the DNA repair mechanism. DNA repair inhibitors are compounds that interfere with the cellular mechanisms responsible for repairing damaged DNA. These inhibitors can be applied to cancer treatment that they make tumor cells more sensitive to other forms of treatments, including radiation, chemotherapy and PDT. These agents can enhance the effectiveness of treatments via preventing DNA repair in cancer cells. Moreover, DNA repair inhibitors have the ability to overcome treatment resistance after PDT. In this review, we highlight the critical responses to PDT-induced DNA damage and the progress made in blocking DNA repair mechanisms through clinical and preclinical studies using nanotechnology or combination therapy. Critically, we highlighted the role of nanomedicine in PDT by offering a platform for the simultaneous delivery of DNA repair inhibitors and photosensitizer (PS). This strategy lead to broaden the therapeutic window for drug delivery and overcoming PDT resistance. Finally, latest findings and studies have been gathered and some suggestions were presented for future studies in this area. This review may help researchers and physicians employ DNA repair inhibitors in PDT for clinical and preclinical studies.