One step closer to personalized cancer treatment

Professor Kim Yoo-sik (back) Ph.D Koo Young-seok (front) of the Department of Chemical & Biomolecular Engineering [Photo provided = KAIST]

KAIST researchers have succeed in discovering gene that can distinguish patients who have or have no effect on anticancer through examine closely on the mechanism of inside the human body of decitabine an anticancer chemotherapy drug used to treat acute myeloid leukemia and Myelodys plastic syndromes.

If patients receive appropriate treatment according to the research it is expected that they will be able to spend less time and cost on treatment significantly.

A joint research team led by professor Kim Yoo-sik of the Department of Biochemical Engineering at KAIST and professor Hong Jun-shik of the Center for Hematological Oncology at the Seoul National University Hospital announced on the 7th that they have found major factors working in anticancer chemotherapy.

The result of the research that Koo Young-seok a PhD student in Department of Chemical & Biomolecular Engineering Researcher Park Joo-hwan of the Seoul National University Hospital and student Cho Ryong of KAIST participated as the 1st author was published on the international journal Proceedings Of The National Academy Of Sciences (PNAS) on March 30th (Thesis name : Noncanonical immune response to the inhibition of DNA methylation via stabilization of endogenous retrovirus dsRNAs).

DNA demethylating agents such as decitabine participate in the DNA replication process and regulate gene expression by removing methyl groups (-CH) which exist in DNA. In particular cancer cells contain much more methylated DNA than the normal cells which inhibits the transcription process that produces RNA from DNA. When cells are treated with a demethylating agent methyl groups are removed from the DNA and various kinds of RNA are produced in the cells.

Among these RNAs regulated by decitabine there is double-stranded RNAs (dsRNA). Originally dsRNAs are produced a lot in virus-infected cells and human cells recognize virus-derived dsRNAs as external substances and cause immune response.

Peculiarly a human innate immune response system that recognizes dsRNA reacts with dsRNA which uses structural features such as dsRNA length or terminal morphology while ignoring nucleic acid ranking information. Due to these characteristics dsRNAs that is produced in the body not necessarily virus-derived dsRNAs can be mistakenly recognized as external substances and cause abnormal immune reactions. In the treatment of cancer the expression amount of dsRNA is increased by the treatment of DNA demethylating agent thereby leading to immune activity by dsRNA and only the cancer cells apoptosis occurs.

The research team studied the genes that increase dsRNA expression by decitabine and regulate the apoptosis by dsRNA. In particular they analyzed various dsRNA-binding proteins that interact with dsRNA focusing on the fact that many of the patients who received the DNA demethylating agent were ineffective to the medicine.

The research team analyzed the expression of Staufen 1 in 46 bone marrow extracts of patients with acute myeloid leukemia and myelogenetic syndrome including azacitidine which were injecte with DNA demethylating agent as well as decitabine and found that the expression of Staufen 1 decreased significantly in patients with no effectiveness. They also found that patients with low Staufen 1 expression had both low overall survival and progression-free survival and that their prognosis was poor.


Kim Yoo-sik of the Department of Biochemical Engineering at KAIST said In this research we not only investigated the effects of simple decitabine anticancer drugs but also tested the effects of decitabine on patients who actually received decitabine. and added By bio-marking genes that we found this time we can predict the effectiveness of DNA demethylating agents such as decitabine and azacitidine which is useful for developing effective personalized cancer treatment strategies.

Meanwhile the research was carried out with the support of the National Research Foundation of Koreas up-and-coming researchers support project and KAISTs future system healthcare research and development project.

On the other hand the research was carried out with the support of the Korea Research Foundations up-and-coming researchers and KAISTs future system healthcare research and development project.

A schematic diagram of chemical anti-cancer therapy mechanism using DNA demethylated agent [Provided = KAIST]

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