According to the recently announced “2021 National Cancer Registration Statistics,” thyroid cancer occurred in 68.6 cases per 100,000 people, ranking first in cancer incidence for three consecutive years. The overall cancer survival rate is 72.1%, but the 5-year relative survival rate for thyroid cancer patients is 100.1%. If it exceeds 100%, it means that more cancer patients survive than the entire population. Thyroid cancer is divided into differentiated thyroid cancer (papillary thyroid cancer, follicular thyroid cancer), undifferentiated thyroid cancer (cancer spreads rapidly and is often inoperable), and medullary thyroid cancer. Papillary carcinoma (PTC), which grows and metastasizes slowly and has low malignancy, accounts for 98-99% of thyroid cancers in Korea, and treatment results are good.
Among them, undifferentiated thyroid cancer (ATC) does not occur often, accounting for approximately 1% of all thyroid cancers, but if left untreated it can lead to death within 3 months, and even for treated patients, the rate survival is more than one year is only 20%.
A national research team has identified the principle of anticancer drug resistance for the first time in undifferentiated thyroid cancer, which shows high resistance to existing anticancer drugs. Consequently, expectations are growing that a new therapeutic strategy can be developed in the field of undifferentiated thyroid cancer, which has been difficult to treat due to the poor efficacy of anticancer drugs.
The joint research team of Professor Seong-soon Hwang, Department of Biomedical Sciences, Yonsei University College of Medicine, and Seok-mo Kim and Hyuk-jun Yoon, Professors of Thyroid and Endocrine Surgery at Gangnam Severance Hospital, conducted the analysis of the genome to find the principle of resistance of undifferentiated thyroid cancer to anticancer drugs.
Accordingly, it was confirmed that glutaminolytic enzyme (GLS) expression was higher in undifferentiated thyroid cancer compared to papillary thyroid cancer.
Cancer cells use glutamine as their main nutrient to survive. Glutamine is considered a cellular energy source alongside glucose, and glutathione (GSH) is synthesized using the glutamine-decomposing enzyme to provide various nutrients and energy to cancer cells. Levels of enzymes that degrade glutamine are elevated in major carcinomas.
The research team predicted that the effectiveness of anticancer drugs would increase if they prevented the supply of nutrients to tumor cells by inhibiting glutamine-breaking enzymes.
However, contrary to expectations, undifferentiated thyroid cancer cells survived even when the glutamine degradation pathway was inhibited.
During this process, the research team discovered that undifferentiated thyroid cancer survives using a “single carbon metabolism mechanism.”
Based on this, an animal experiment was conducted in which a glutaminolytic enzyme inhibitor (BPTES) and an inhibitor (CBR-5884) that inhibits PHGDH, a key enzyme in the mechanism of single carbon metabolism, were simultaneously administered .
As a result, the balance of reactive oxygen species (ROS) that maintain tumor cells was disrupted, promoting tumor cell death, and it was observed that the anti-tumor effect was improved by approximately 50% compared to use of a single existing anticancer drug.
Furthermore, the research team conducted further genomic tests and confirmed that the mechanism of single carbon metabolism strengthens as thyroid cancer progresses from papillary thyroid cancer to undifferentiated thyroid cancer.
Professor Seong-soon Hwang said, “Research to develop new drugs that inhibit glutamine degradation and single-carbon metabolism mechanisms is actively underway overseas, but has not yet received much attention in Korea.” the most important factor in cancer drug resistance, so that it can be controlled.”We will conduct follow-up research to develop new drugs,” he said.
Professor Kim Seok-mo said: “Gangnam Severance Hospital is treating the most incurable undifferentiated thyroid cancer in the country” and added: “I hope that the new treatment strategy of combined administration which simultaneously inhibits the glutaminolytic enzyme and the PHGDH will be a great help.” to many patients with undifferentiated thyroid cancer.”I do it,” he said.
The research findings were published in “Cell Death & Disease (IF: 9.1)” by Nature Publishing Group (NPG).
Daeik Kwon, medical journalist>
2024-01-16 03:09:49
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