SEOUL, April 23 (AJP) - A joint research team from the Korea Advanced Institute of Science and Technology, Uijeongbu Eulji University Hospital, and Ulsan National Institute of Science and Technology has identified a new molecular mechanism that controls how chronic myeloid leukemia responds to anticancer drugs, the state-operated research institute located in the central city of Daejeon said Thursday, April 23, 2026.
Chronic myeloid leukemia is caused by an abnormal protein called BCR::ABL1 that sends continuous growth signals to cells, causing them to multiply. While targeted drugs are the standard treatment to block this protein, some patients develop resistance or show a low response to the medication.
The researchers focused on how these drugs affect the internal "protein factories" of cancer cells, known as ribosomes. They found that the treatment causes these ribosomes to jam and crash into each other, a process called ribosome collision. This creates intense internal stress that leads the cancer cell to destroy itself.
A protein named ZAK was identified as the key sensor for these collisions. The study found that ZAK plays two opposing roles depending on the environment. Under normal conditions, it assists cancer growth by connecting with certain signals. However, once drug treatment begins, it switches to a monitoring role that triggers cell death.
The team verified this mechanism by analyzing cancer cells from leukemia patients. They found that using additional drugs to increase ribosome collisions significantly improved the effectiveness of the treatment. In contrast, cells with low ZAK function were more likely to resist the anticancer drugs.
These findings suggest that a patient's ZAK activity levels could be used to predict how they will respond to treatment. It also opens the door for new combination therapies that could help patients who have built up a resistance to current drugs.
"This research shows how important the process of a cell detecting abnormal protein synthesis and converting it into a death signal is for treatment," Professor Lim Jung-hoon said.
"Since we have confirmed that ribosome collisions are the key switch that determines the death of cancer cells, we plan to expand our research to various types of cancer," Dr. Park Ju-min said.
(Reference Information)
Journal/Source: Leukemia
Title: BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia
Link/DOI: https://bit.ly/4vIofWw
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