Clinical development and potential of photothermal and photodynamic therapies for cancer

Light-activated, photosensitizer-based therapies have been established as safe modalities of tumour ablation for numerous cancer indications. Two main approaches are available: photodynamic therapy, which results in localized chemical damage in the target lesions, and photothermal therapy, which results in localized thermal damage. Whereas the administration of photosensitizers is a key component of photodynamic therapy, exogenous photothermal contrast agents are not required for photothermal therapy but can enhance the efficiency and efficacy of treatment. Over the past decades, great strides have been made in the development of phototherapeutic drugs and devices as cancer treatments, but key challenges have restricted their widespread clinical use outside of certain dermatological indications. Improvements in the tumour specificity of photosensitizers, achieved through targeting or localized activation, could provide better outcomes with fewer adverse effects, as could combinations with chemotherapies or immunotherapies. In this Review, we provide an overview of the current clinical progress of phototherapies for cancer and discuss the emerging preclinical bioengineering approaches that have the potential to overcome challenges in this area and thus improve the efficiency and utility of such treatments. Photodynamic and photothermal therapies hold promise in the local treatment of cancer although, arguably, their full potential has not yet been achieved. Herein, the authors review the current clinical progress of these phototherapies and discuss the bioengineering approaches that are being explored to overcome challenges and thereby improve such treatments. Key points Photodynamic therapy is predicated on the localized activation of photosensitizers within tumours in order to induce chemical damage and thus the death of tumour cells; this approach has been used in the clinic for >40 years for the treatment of diverse cancers, including superficial skin lesions and oesophageal and lung tumours. Photothermal therapy (PTT) agents, which can be used to increase the efficiency of localized light-based heating and ablation of tumour tissues, have not yet been tested in large clinical trials; laser ablation without PTT agents has been used clinically. Relative to single-modality approaches, drug–device combinations complicate clinical development; therefore, compelling efficacy and safety benefits are needed to support the use of such platforms in favour of com