A domestic research team has developed a PROTAC nanotherapeutic that simultaneously degrades an immune-metabolism–related protein in intractable breast cancer and uses light to kill cancer cells. PROTAC refers to a small-molecule compound that induces the degradation of disease-causing proteins.
The National Research Foundation of Korea (NRF) said on the 29th that a research team led by Senior Researcher Sim Man-gyu at the Korea Institute of Science and Technology (KIST) and a team led by Park Ju-ho, a professor in the Department of Biomedical Science and Engineering at Konkuk University, developed a new nanotherapeutic, "NanoTAC," that can treat triple-negative breast cancer.
Triple-negative breast cancer is a type of breast cancer that progresses rapidly and carries a high risk of metastasis and recurrence. The research team applied PROTAC, which has recently drawn attention in clinical settings, to immunotherapy for triple-negative breast cancer and developed the nanotherapeutic NanoTAC that can deliver it effectively to tumor tissue.
NanoTAC was developed by incorporating a PROTAC capable of continuously degrading a key protein involved in intracellular immune metabolism and a photosensitizer that can maximize immunogenicity within tumor tissue. A photosensitizer is a drug that responds to light.
When NanoTAC was administered to an animal model of triple-negative breast cancer, it accumulated in the tumor and was cleaved by tumor-specific enzymes, releasing the PROTAC and photosensitizer separately. The PROTAC degraded the target protein to suppress the function of cancer cells, and the photosensitizer, when exposed to light, inhibited tumor growth, recurrence, and metastasis through an immune response.
Senior Researcher Sim Man-gyu noted, "A nanomedicine technology that maximized immunogenicity within cancer cells through the synergistic effect of PROTAC and photodynamic therapy," adding, "We expect NanoTAC could become a new foundational anticancer immunotherapy technology for treating intractable cancers."
The findings were published on the 26th in the international journal "Signal Transduction and Targeted Therapy."
References
Signal Transduction and Targeted Therapy (2025), DOI: https://doi.org/10.1038/s41392-025-02405-6