A research team at Yonsei University College of Medicine has identified a new compound that selectively attacks drug-resistant metastatic cancer cells while sparing healthy cells, a breakthrough that could open a new avenue for treating cancers that no longer respond to conventional therapies.
The university announced on June 5 that a team led by Professor Park Ki-cheong of the Department of Surgery discovered the experimental compound PPS03, which demonstrated anti-cancer activity against metastatic tumors resistant to existing treatments while minimizing damage to normal cells.
The findings were published in the latest issue of the international journal Biomaterials. The study involved Professor Lim Jin-ho of Gangnam Severance Hospital, Professor Choi Kyung-hwa of Bundang CHA Hospital and biotechnology company Therapeutics NMC.
Cancer cells that develop resistance to treatment often gain the ability to spread to other organs, making metastatic disease one of the most difficult challenges in oncology.
Both healthy and cancerous cells generate reactive oxygen species (ROS) during metabolic processes. While moderate levels of ROS support cellular growth and signaling, excessive accumulation can trigger cell death. Researchers worldwide have explored ways to increase ROS levels in tumors to destroy cancer cells, but these approaches have often damaged healthy cells as well, leading to significant side effects.
The Yonsei team focused on a process known as macropinocytosis, a mechanism through which cells absorb surrounding fluid and nutrients. The researchers found that metastatic cancer cells frequently engage in macropinocytosis, whereas normal cells do so far less often.
Using this difference, the team demonstrated that metastatic cancer cells selectively absorbed PPS03 while healthy cells largely did not. Once inside the cancer cells, iron ions and selenomethionine ions contained in PPS03 dramatically increased ROS levels, ultimately triggering cancer cell death.
The researchers validated the mechanism using cancer cells derived from liver cancer patients whose tumors had developed resistance to existing anti-cancer therapies.
“We are currently preparing clinical studies,” Park said. “If commercialized, this technology could become a game changer in the global oncology market.”
The global cancer drug market is currently valued at approximately $250 billion and is projected to expand at a compound annual growth rate of 6% to 12%, potentially reaching as much as $500 billion by the mid-2030s.
As drug resistance remains one of the biggest obstacles in cancer treatment, efforts to overcome treatment-resistant tumors have become a major focus for both academic researchers and the pharmaceutical industry.
