Recently, Professor Li-Ming Chen's research group has made important progress in breast cancer brain metastasis mechanism research. The research results were published online under the title of “A brain-enriched lncRNA shields cancer cells from immune-mediated killing for metastatic colonization in the Brain” in the international journal PNAS by Li-Ming Chen as the corresponding author, with Weiguang Liu as the first author, Peng Sun, director of Zhongshan Cancer Hospital, as the co-first author.

 

 

Brain metastasis is a common complication in advanced cancer patients, with limited treatment options, and breast-to-brain metastasis (B2BM) is one of the major types of brain metastasis. Taking breast cancer as a model, this study focused on the following four aspects: First, “brain metastasis oncogenic long noncoding RNA” (BMOR) was discovered and first named for the first time; Second, a novel mechanism of tumor immune escape (BMOR-IFR3 signaling axis) was revealed; Third, an entirely new therapeutic agent (locked nucleic acid, LNA-BMOR) was provided; Fourthly, the theory of "three modes" of tumor immune escape was summarized and put forward (the mode of "avoiding immune recognition", the mode of "inhibiting immune activation" and the mode of "escaping immune-mediated death of cancer cells"). This study provides a new idea for the study of brain transfer mechanism and intervention strategies, and provides a basic theoretical framework for the study of tumor immune escape.

Professor Li-Ming Chen named the discovered gene, BMOR, and first demonstrates the tissue specificity of long chain noncoding RNA distal lead to specific brain metastases of cause and effect, effective targeted therapy drugs developed on this basis has great treatment effect, which further in combination with CpG treatment strategy, can even cure some brain cancer in mice. Mechanistic studies suggest that BMOR inhibition of IRF3 prevents cancer cells from being immunologically killed in the brain microenvironment. This new mechanism of tumor immune escape provides important evidence support for summarizing and putting forward the “three models” theory of tumor immune escape. This research provides new ideas for solving global problems such as tumor brain metastasis, long non-coding RNA research, and tumor immune escape mechanism and intervention research, which is helpful for mankind to conquer cancer.

Over the past five years, the team led by professor Li-Ming Chen has discovered and revealed the most broad-spectrum mechanism of triple negative breast cancer malignant growth to date (prKD3-CLU signaling axis covering nearly 90% of triple negative breast cancer) and developed targeted intervention strategies (PNAS, 2017; Adv. Sci., 2021); Discovered and developed the first breast cancer immune prevention drug patent in the world (new drug authorized invention Patent Number: ZL 201910921285.5, 2022), etc.