Sungkyunkwan University, KIST researchers develop innovative anticancer platform

A Sungkyunkwan University research team has developed an innovative cancer treatment platform in collaboration with researchers at the Korea Institute of Science and Technology (KIST).

Sungkyunkwan University said the platform is designed to simultaneously identify cancer cells and the surrounding cells that support them and block communication between the two at its source by suppressing the production of extracellular vesicles.

The team was led by professor Yang Yoo-soo of the university’s department of integrative biotechnology. It collaborated with a KIST research team headed by Dr. Shim Man-kyu.

Cancer does not grow through the efforts of cancer cells alone. Surrounding the cancer cells are cancer-associated fibroblasts and various immune cells that act like collaborators, forming a complex community known as the tumor microenvironment.

These cells communicate with one another by exchanging tiny packages called extracellular vesicles, which carry signaling molecules between cells.

Through this exchange, cancer cells gain advantages that promote their growth and spread to other organs while increasing their resistance to anticancer drugs.

Conventional cancer treatments have largely focused on attacking the cancer cells themselves, making it difficult to completely break the vicious cycle in which surrounding cells continue to support and protect cancer cells.

To address this problem, the research team focused on a specific protein, epidermal growth factor receptor, that is commonly found on the surface of both cancer cells and fibroblasts that support tumor growth.

Using EGFR as a targeting signal, the team developed an antibody-drug conjugate designed to precisely seek out these cells and deliver a drug that selectively degrades a specific protein inside the cells, cyclooxygenase-2, much like a molecular vacuum cleaner.

Once the precision-guided drug enters cancer cells and fibroblasts, it effectively shuts down the production of extracellular vesicles — tiny delivery packages that carry and transmit signaling molecules between cells.

As a result, the “secret communication network” through which cancer cells and surrounding cells supported each other and fueled tumor growth was disrupted.

Experiments in cells and animal models showed that the cancer cells’ ability to migrate was significantly reduced, while the tumor-supporting environment around them was transformed into an environment more hostile to tumor growth. The growth of the tumors was also clearly suppressed.

The achievement is significant in that it moves beyond conventional treatments that target cancer cells alone.

By combining precision-targeting antibody technology with targeted protein degradation, the approach opens a potential new therapeutic avenue for disrupting the tumor-supporting ecosystem that fuels cancer growth.

“Cancer cells constantly communicate with surrounding cells, like operators exchanging radio messages, to create an environment that favors their own survival and growth,” professor Yang said

“This study presents a new precision anticancer strategy that simultaneously targets cancer cells and their helper cells while disrupting the malignant communication network between them, thereby destabilizing the tumor tissue as a whole,” she added.

The findings were published online Sept. 17 in the Journal of the American Chemical Society under the title “Receptor-Guided Targeted Protein Degradation Collapses Extracellular Vesicle-Driven Tumor-Stroma Crosstalk.”

The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea.