Synergistic effects of combining phototherapeutics with traditional treatment modalities in oncology

Phototherapeutic methods like photodynamic therapy (PDT), photothermal therapy (PTT) and photodecaging have emerged as promising modalities for cancer treatment. Phototherapeutics are activated by light and thereby generate reactive oxygen species (ROS), heat, or release a caged, toxic carry-on. Their distinct advantages of spatial and temporal control preserve healthy tissue while promising a minimal invasive alternative to traditional therapeutic approaches. When combined with each other or with other treatment modalities like chemotherapy, immunotherapy, etc., they can exert a synergistic effect that enhances their overall efficacy by improving targeting and destroying cancer cells. Given the rapid expansion of combination therapies that incorporate phototherapeutic elements, it is crucial to gain an understanding of the most important phototherapeutic methods and their synergistic effects when used in combination. This review provides a comprehensive overview of these combinations, focusing on the benefits such as overcoming drug resistance, improving targeting, and minimizing side effects, while also addressing the current challenges that must be overcome. The clinical translation of these combination therapies is also explored, with particular attention to the regulatory hurdles and advancements required to bring these promising treatment modalities into clinical practice.