New approaches to increasing the effectiveness of photodynamic therapy in oncology
Photodynamic therapy (PDT) is on the list of widely used methods for treating several types of cancer, including mesothelioma, skin, lung, brain, digestive and genitourinary cancers. In PDT, specific agents (photosensitizers) are injected into the body and accumulate in the tumour. When exposed to light of a certain wavelength, they produce reactive oxygen species that have a toxic effect on the tumour cell causing its death. This type of therapy is already used in the clinical practice, but the search for ways to increase the effectiveness of PDT is still relevant.
Currently, scientists believe that the most promising approach is to activate the death of tumour cells through the immunogenic pathway. The immune system is activated due to the release of specific molecules (DAMPs) from the dying tumour cells, which contribute to the attraction and maturation of antigen-presenting cells (dendritic cells) and the subsequent activation of a specific immune response. This response contributes to the fight against remaining malignant cells, which determines the long-term remission or even complete recovery of the patient. It is now known that photodynamic treatment can activate several types of cell death, but not all of them have immunogenic properties.
In 2020, a joint study by scientists from the Institute of Biology and Biomedicine of the National Research Lobachevsky University of Nizhny Novgorod, the University of Ghent (Belgium) and the University of Bologna (Italy) led by Professor Dmitry Krysko found that a newly discovered form of cell death, ferroptosis, has certain immunogenic properties. A model of prophylactic vaccination by dying ferroptotic tumour cells has shown a significant slowdown in the growth of the experimental tumour (click here for the full text article). Subsequently, Prof. Dmitry Krysko together with Dr. Tatiana Mishchenko and Dr. Maria Vedunova of the UNN Institute of Biology and Biomedicine, with the participation of Dr. Irina Balalaeva, an expert in photodynamics, conducted analysis of the experimental data and results of other world-class research groups, demonstrating a subtle synergy between ferroptosis reactions and photodynamic effects.
"We believe that the products of the photodynamic reaction may serve as a source for activating and enhancing ferroptotic death of tumour cells. Given the immunogenic properties of ferroptosis, developing a way to activate this form of cell death in PDT can be considered as a powerful alternative strategy to improve the effectiveness of the therapy by avoiding tumour resistance to other types of cell death (apoptosis, necroptosis)," says Dmitry Krysko.
In a recent article "Ferroptosis and Photodynamic Therapy Synergism: Enhancing Anti-Cancer Treatment" published in the highly acclaimed international journal Trends in Cancer (impact factor 11.99), the researchers have presented their hypothesis to the scientific community (click here for the full text article). Since photodynamic therapy is a minimally invasive and minimally toxic procedure, improving this type of therapy is one of the most promising directions in the fight against tumours and metastases. Currently, scientists are
continuing active research to study the mechanisms of ferroptosis and the possibility of its activation by photodynamic treatment.