New compound from Yonsei University School of Medicine attacks only cancer cells

Low side-effect profile positions it as alternative to existing anticancer drugs

(From left) Park Ki-chung, a professor in the Department of Surgery at Yonsei University College of Medicine; Lim Jin-hong, a professor in the hepatobiliary and pancreatic surgery division at Gangnam Severance Hospital; and Choi Kyung-hwa, a professor at Bundang CHA Hospital. [Severance Hospital]
(From left) Park Ki-chung, a professor in the Department of Surgery at Yonsei University College of Medicine; Lim Jin-hong, a professor in the hepatobiliary and pancreatic surgery division at Gangnam Severance Hospital; and Choi Kyung-hwa, a professor at Bundang CHA Hospital. [Severance Hospital]

Severance Hospital announced Friday that a research team at Yonsei University College of Medicine has discovered a compound capable of treating drug-resistant metastatic cancer.

The team — led by Park Ki-chung, a professor in the Department of Surgery at Yonsei University College of Medicine, and joined by Lim Jin-hong of Gangnam Severance Hospital's hepatobiliary and pancreatic surgery division, Choi Kyung-hwa of Bundang CHA Hospital, and researchers from Therapeutics NMC — identified a new compound, PPS03, that is effective against metastatic cancers resistant to existing anticancer drugs while leaving normal cells unharmed, reducing the risk of side effects.

The findings were published in the latest issue of the international journal Biomaterials (impact factor: 12.9).

Cancer cells that develop resistance to anticancer drugs can spread to other organs. Both normal and cancerous cells produce reactive oxygen species (ROS) during metabolic processes. ROS serve as a signal of cell growth, but when they accumulate beyond a certain threshold, they trigger cell death.

Researchers worldwide have sought to exploit this by increasing ROS levels in cancer patients to kill tumor cells. The problem is that normal cells also produce ROS, meaning attempts to destroy cancer cells can inadvertently damage healthy tissue as well.

Park's team focused on a phenomenon called macropinocytosis, which occurs far more commonly in metastatic cancer cells than in normal cells. Macropinocytosis is the process by which cells absorb surrounding fluid to obtain nutrients.

The researchers found that metastatic cancer cells took up PPS03 through macropinocytosis, while normal cells did not absorb the compound.

They also confirmed that iron ions and selenomethionine ions in PPS03 — absorbed by metastatic cancer cells during macropinocytosis — elevated ROS levels and triggered cancer cell death.

The team demonstrated this effect using cancer cells obtained from tumor tissue taken from liver cancer patients whose disease had become resistant to existing anticancer drugs.

PPS03 is significant because it acts selectively by exploiting the metabolic characteristics of metastatic cancer cells. Unlike conventional ROS-based anticancer approaches, which carry the risk of damaging normal cells, this research leverages the cancer cells' own nutrient-absorption process to improve both therapeutic efficacy and safety.

"PPS03 not only showed effectiveness against metastatic cancers resistant to existing anticancer drugs, but it also spares normal cells, which means side effects can be reduced," said Lim Jin-hong.

Park Ki-chung added that the compound, whose metastatic cancer-specific anticancer effect was confirmed in this study, is currently being prepared for clinical trials and "will act as a game changer in the global anticancer drug market once commercialized."


woo@heraldcorp.com