Korean researchers have become the first in the world to identify the process by which lung cancer cells transform their surroundings into "soil favorable for cancer" before they begin full-scale growth. The findings are expected to pave the way for a new strategy that blocks cancer at its earliest stage, moving beyond the conventional approach of treating cancer after it develops.
According to the scientific community on Tuesday, a joint research team led by Professor Choi Jin-wook of the Department of Life Sciences at Gwangju Institute of Science and Technology (GIST) and Professor Lee Ju-hyun of Memorial Sloan Kettering Cancer Center (MSK) in the United States has uncovered the structure of the chain reaction between cells that occurs in the early stages of lung cancer development. The findings were published online in Nature, the world's top-tier academic journal, on April 22.
Lung adenocarcinoma rarely shows early symptoms and is usually detected only after the cancer has significantly progressed. While the academic community has been studying how mutated cells develop into cancer, the specific process by which mutated cells tame surrounding normal tissue into a cancer-friendly environment has remained shrouded in mystery.
The research team used single-cell analysis technology and three-dimensional artificial organs known as "organoids" to track the "conversation" between cancer cells and neighboring cells.
The findings show that lung cancer develops through three major stages. First, mutated lung stem cells secrete large amounts of a signaling substance called amphiregulin (AREG), sending aggressive signals. Then, the surrounding cells that receive these signals lose their tissue repair function and trigger a "fibrosis phenomenon" that hardens the tissue, creating soil optimized for cancer growth. Finally, this environment draws in immune cells (macrophages) that induce an inflammatory response, and these inflammatory signals in turn promote cancer cell growth, completing a "vicious cycle."
Notably, the research team confirmed that when the amphiregulin signal, the key link in this chain reaction, was blocked with drugs, the cancer-inducing environment failed to form, and early-stage lung cancer development was significantly suppressed. In collaboration with the team of Professor Park Moo-suk at Yonsei University's Severance Hospital, the team also demonstrated that the same mechanism operates in lung tissue models from actual patients, confirming the potential for it to work in clinical settings.
"This research identified the vicious cycle in which cancer cells and their surrounding environment support each other," Professor Choi Jin-wook said. "It holds great significance in that we have discovered a new therapeutic target that can block cancer development at its very root."
