Every cell in your body carries a set of instructions written in DNA. Sometimes, a tiny typo in those instructions can cause a cell to grow out of control — that is cancer. One of the most common typos causing cancer is called KRAS(G12D), found in pancreatic, colorectal, and lung cancers. For decades, this mutation sat inside cells where antibodies — the guided missiles of medicine that seek out diseased cells — simply could not reach it. Scientists called it an "undruggable target."
Now, researchers at KAIST University in Daejeon, South Korea, have found a way to give those antibodies the "eyes" they need to see hidden cancer mutations.
Professor Byung-Ha Oh from the Department of Biological Sciences led a team that combined computer design with lab experiments to create a new antibody. This antibody can recognize and attach to cancer cells carrying the KRAS(G12D) mutation while leaving healthy cells mostly alone. The work was published in the journal Molecular Therapy.
The team at Therazyne, a startup born from KAIST, focused on how cells naturally break down old or damaged proteins into tiny fragments. When cancer cells process the mutated KRAS(G12D) protein, they also chop it into pieces. Some of these pieces get displayed on the outside of the cell, like a flag saying "I am cancer." The researchers designed an antibody that can read that flag.
Think of it like teaching a guided missile to recognize a specific disguise worn only by cancer cells. Professor Oh compared it to giving antibodies the eyes of T cells — the immune system's scouts that scan the body for threats. In lab tests, the new antibody selectively killed cancer cells with the mutation while showing little to no reaction to normal cells or other proteins.
This matters because antibodies have long been used to treat diseases, but they could not peek inside cells where many cancer mutations hide. The new approach opens a door for treating tumors that were previously too difficult to target. The researchers are now testing their antibody in animal models to see if it works in living beings.
"The antibody developed in this study can selectively identify only cancer cells carrying the KRAS(G12D) mutation, demonstrating the potential for precision antibody therapeutics that minimize damage to normal cells," Professor Oh said. He added that the computer design methods used in this research could be applied to target not just KRAS but a wide range of other cancer mutations.
The team expects this technology could become a platform for developing next-generation therapies — medicines that are more precise, attacking only the cells that need to be stopped while leaving healthy tissue intact.