Korean researchers develop new classification system for oral cancer’s precision treatment

A Korean research team has used patient-derived organoids to classify oral cancer morphologically and identify the prognosis and drug response characteristics of each type.

The National Cancer Center (NCC) announced on Tuesday that its research team has developed a technology to classify oral cancer morphologically using “mini-organs (organoids)” cultured in the laboratory from patient-derived oral cancer cells.

Professor Kim Yun-hee of the NCC’s Molecular Imaging Research Department, Professor Choi Sung-weon of the Oral Oncology Clinic at the Rare Cancer Center, Professor Shin Dong-kwan and Drs. Lee Mi-rim, Kang Soo-min, and Lee Jong-hyun of the Cancer Biomedical Science Department conducted the study. The research team also included Professor Kwon Ik-jae of the Department of Oral and Maxillofacial Surgery at Seoul National University School of Dentistry.

Oral cancer is a rare and intractable cancer with a high recurrence rate and a poor prognosis, with a five-year survival rate of less than 30 percent in advanced stages. Additionally, it has a low rate of genomic mutations and unclear molecular subtypes, which makes it challenging to identify effective treatment targets.

To overcome these limitations, the research team created 76 types of cancer organoids from tissue samples of oral cancer patients. This marks the world's largest patient-derived cancer organoid bank for oral cancer.

They then classified the organoids into three subtypes based on their morphological characteristics: normal-like, dense, and grape-like. This classification clearly distinguished the subtypes according to clinical prognosis.

Notably, dense and grape-like organoids exhibited a high TP53 gene mutation rate of over 87 percent. They also showed increased tumor mutation burden (TMB), indicating a strong correlation with patient groups at high risk of recurrence and poor survival rates. In contrast, normal-type organoids were identified as a subtype with excellent responsiveness to anticancer drugs and a favorable prognosis.

The research team compared the drug response characteristics of each organoid subtype based on genomic and transcriptomic data. The results showed that dense-type organoids exhibited resistance to multiple targeted anticancer drugs. However, when combined with ATR inhibitors (BAY1895344) targeting the DNA damage response (DDR) pathway and the standard chemotherapy drug cisplatin, a strong effect was observed. The research team explained that this suggests the potential for a new combination therapy strategy for patients with difficult-to-treat oral cancer, where treatment options are limited.

“This study overcame the challenge of establishing treatment targets due to the low genomic mutation rate and high heterogeneity of oral cancer by utilizing organoid-based morphological classification and multi-omics integrated analysis,” Professor Kim, the lead researcher, said. “It serves as a representative example of precision medicine research linking patient-tailored treatment strategies.”

Professor Choi said, “This study demonstrates the potential for personalized oral cancer treatment by expanding organoid-based classification reflecting patient tumor characteristics to drug response prediction. It could serve as a turning point in providing practical treatment options for patients with rare and intractable oral cancers.”

This research was supported by the NCC's Public Cancer Research Project, the National Research Foundation of Korea's Mid-Career Research Project, and the Multi-Ministry National Life Science Research Resource Advancement Project. The research results were published in the international academic journal, “Cell Reports Medicine.”