An image captioned “Research image elucidating the dual role of leukemia chemotherapy drug (AI-generated, provided by KAIST) / News1” was provided, along with a report stating that a South Korean research team has discovered a new mechanism by which chemotherapy drugs kill cancer cells.
KAIST announced that a collaborative research team, led by Professor Lim Jeong-hoon from its Department of Biological Sciences, Professor Kim Dong-wook from Uijeongbu Eulji University Hospital’s Hematologic Oncology Center, and Professor Kim Hong-tae from UNIST’s Department of Biological Sciences, has identified a new molecular mechanism regulating the response to chronic myeloid leukemia chemotherapy drugs.
Chronic myeloid leukemia originates from an issue with hematopoietic stem cells. When there is a genetic abnormality in these cells, an abnormal protein called ‘BCR::ABL1’ is produced, functioning like a faulty switch that continuously sends growth signals to cancer cells. Currently, ‘targeted chemotherapy’ that inhibits this protein’s function is used for treatment. However, some patients develop drug resistance over time, reducing the treatment’s efficacy.
The core of the recent research lies in a different ‘method of cancer cell death.’ Previously, targeted chemotherapy was known to act by inhibiting the function of specific proteins that cause cancer. The research team discovered that, in addition, the drug induces ‘ribosomal collisions’ during the protein production process within cells, causing significant stress that ultimately leads the cancer cell to self-destruct. Ribosomes, which act as ‘protein factories,’ operate sequentially during protein synthesis, and when the leading ribosome stops or slows, subsequent ribosomes may collide.
The team identified that the ‘ZAK protein’ plays a crucial role in this process. Normally, ZAK assists cancer cell growth, but during chemotherapy, it senses ribosomal collisions and induces cell death, performing dual roles. In experiments with cancer cells derived from leukemia patients, artificially increasing ribosomal collisions significantly enhanced the anticancer effect, whereas reducing ZAK function led to decreased drug response.
The researchers emphasized that the findings provide an explanation of drug resistance origins attributed to ‘ZAK function anomalies’ and ‘ribosomal stress response,’ and expressed hope that the results will lead to the development of customized treatment strategies and combination therapies tailored to individual patients.