The National Cancer Center has presented a new therapeutic principle that could overcome drug resistance, the biggest challenge in pancreatic cancer treatment. The approach enhances the effectiveness of anticancer drugs by cutting off the "energy supply" that keeps cancer cells alive.
The National Cancer Center announced Thursday that a research team led by Dr. Kim Soo-youl, together with a clinical team headed by Professor Woo Sang-myung, has discovered that suppressing "fatty acid oxidation," the energy source of cancer cells, can neutralize anticancer drug resistance. The research drew attention when it was recently presented at the American Association for Cancer Research (AACR).
Cancer treatment is difficult because cancer cells do not die even under drug attack and revive through "resistance." When hit by anticancer drugs, cancer cells face an energy shortage, but they survive through a process called "autophagy," in which they break down their own components to generate energy.
Previous approaches attempted to block the early stages of autophagy, but cancer cells revived by activating other pathways. The research team discovered that the process by which cancer cells burn "fatty acids" to produce energy when energy is scarce — namely, fatty acid oxidation — is the key to resistance.
In simple terms, when anticancer drugs are administered, cancer cells survive by using fat instead of glucose as fuel, and if this pathway is blocked, they can no longer hold out and die. When the research team administered anticancer drugs together with a fatty acid oxidation inhibitor, they confirmed that cancer cells were completely eliminated.
Based on this principle, the research team also developed a new drug candidate, "KN510713," which selectively inhibits only fatty acid oxidation. It is characterized by reduced liver toxicity, which had been a limitation of existing inhibitors, and is currently undergoing Phase 2 clinical trials.
"This research is significant in that it targets the common energy metabolism of cancer cells rather than specific genetic mutations," Dr. Kim Soo-youl said. "It could be applied not only to pancreatic cancer but also to the treatment of various intractable cancers."
The findings were published in the April issue of the international journal Cancer Research.
