Researchers at Seoul National University Bundang Hospital (SNUBH) and Samsung Medical Center (SMC) said they have become “the world’s first” to discover how normal gallbladder epithelial cells evolve from precancerous lesions to primary gallbladder or metastatic gallbladder cancer cells.
The team, led by Professors Kim Ji-won, Kang Min-su, Na Hee-young at SNUBH and Ahn Soo-min at SMC, emphasized that the research results will help doctors select a more effective targeted anti-cancer drug.
The gallbladder is a sac that concentrates and stores bile which aids in the digestion of fats. The world average incidence rate of gallbladder cancer is low, ranking 20th among cancers. However, there is a high incidence rate in a few countries, including Korea, Thailand, China, and Chile.
While the recent advent of the latest therapy targeting mutations in cancer-related genes has helped better treat patients, it is essential to understand the drug resistance, development, and evolution mechanism of these cancer cells.
However, there had been no proper studies on the pathogenesis and metastasis of gallbladder cancer.
Accordingly, the team conducted a rapid autopsy of two patients who died of metastatic gallbladder cancer and secured normal tissues, precancerous lesions, and primary cancer and metastatic cancer lesions.
Afterward, the team conducted additional analysis on nine gallbladder cancer patients to identify the pathogenesis and metastasis of gallbladder cancer.
As a result, the team confirmed that the distribution of mutations in cells from precancerous lesions, which are the precancerous stage, was very diverse.
According to the research team, one precancerous lesion is composed of several cell populations according to the distribution of mutations in cells constituting the lesion.
As the clones compete with each other, the winning clone undergoes an evolutionary process in which it is transformed into a primary carcinoma.
The clones constituting the evolved primary carcinomas also make several new clones that acquire new mutations over time and sometimes metastasize into other organs.
The research team said it is difficult to treat gallbladder cancer due to such a complex process continuously occurring inside the body of gallbladder cancer patients,
Thus, when treating gallbladder cancer, using the optimal target anticancer drug by tracking the temporal/spatial changes of possible tumor clones can maximize the treatment effect, the research team noted.
“Representative gene mutations of gallbladder cancer exist from the precancerous stage, but many of the mutations are observed only in some cancer cells,” Professor Kang said. “To maximize the effect of targeted anticancer drugs, it is necessary to check the existence of mutations in cancer genome data and track the temporal and spatial changes of tumor clones harboring the mutation.”
Professor Kim also said, “The study has made it possible to understand the pathogenesis and metastasis of gallbladder cancer at a deeper level.”
However, to connect the results of this study to treatment effects in actual patients, it is essential to develop various new drugs that can neutralize each gene mutation, Kim added.
The study result was published in eLIFE.