A Severance Hospital research team has opened ways for customized cancer treatment by developing a method to analyze the functions of many tumor mutations at once.
According to the hospital, the sequence of human genes has four bases, also referred to as a base sequence. While various researchers have identified millions of mutations in the nucleotide sequences of cancer patients, not all mutations affect the formation of malignant tumors.
To quickly treat cancer from the beginning, it is effective to establish a treatment plan based on some tumor mutations that develop into cancer.
Hospitals currently statistically analyze tumor mutations and identify the mutations that have influenced cancer development. However, this method could not elucidate the causal relationship and had limitations as hospitals could only conduct the observation of a small number of tumor mutations with a high frequency of detection.
To resolve this issue, the team, led by Professors Kim Hyong-bum, Kim Young-gwang, and Doctor Lee Seung-ho, developed a technology to introduce tumor mutations into normal cells in large quantities using nucleotide sequence and nucleotide conversion gene scissors.
Because base-transformation gene scissors only target and analyze target tumor mutations, the team found that it could evaluate the function of tumor mutations more accurately than before. With this method, the team found that it could evaluate about 30,000 tumor mutations to identify cancer-causing mutations.
Based on the method, the team also confirmed many tumor mutations resistant to the anticancer drug Apatinib.
The epidermal growth factor tumor mutation (T790M) is a mutation that shows resistance to Apatinib and activates lung cancer cells. After generating a tumor mutation related to epidermal growth factor, the team introduced a large amount of normal cells one-to-one. Then, it administered Apatinib to observe the change in the number of cells.
As a result, the team verified the effectiveness of the excavation method by reconfirming that cells with epidermal growth factor mutation (T790M) actively proliferate despite the administration of Apatinib.
“By evaluating the function of many tumor mutations at once, it is now possible to distinguish tumor mutations that lead to cancer,” Professor Kim Hyong-bum said. “Based on this, we plan to strengthen the development of tumor mutation treatments further.”
Professor Kim Young-gwang also said, “With this research, we have developed a technology to identify tumor mutations that cause resistance to anticancer drugs.”
As a technology that can easily detect tumor mutations resistant to an anticancer drug, the team expects that the research can help develop anticancer drugs in the future.
The results of the research were published in Nature Biotechnology.