China News Service, Shanghai, April 7 (Reporter Chen Jing) The reporter learned on the 7th that Chinese medical experts have finally found the "culprit" and mechanism of resistance to chemotherapy for triple-negative breast cancer patients that has troubled clinical practice for a long time.
Professor Wang Hongxia, Director of the Department of Internal Medicine, Fudan University Cancer Hospital, led a research team to identify a new drug-resistant subpopulation of fibroblasts in the tumor microenvironment, which is closely related to the failure of chemotherapy. Based on this major discovery, the team developed a combination treatment strategy targeting relevant signals to solve the problem of patients' chemotherapy resistance. It is reported that the latest issue of Science sub-journal Science Translational Medicine published the research results of Chinese experts.
The latest issue of Science Translational Medicine published the research results of Chinese experts. (Photo courtesy of Fudan University Cancer Hospital)
It is reported that triple-negative breast cancer is known as the "most toxic breast cancer" because of its highest degree of malignancy, short patient survival time, and lack of effective treatment targets. In the treatment of triple-negative breast cancer, chemotherapy drugs are widely used, and the problem of drug resistance is becoming increasingly serious, especially in some patients whose tumors progress rapidly after chemotherapy. However, the molecular mechanisms behind this phenomenon are unclear. Finding the mechanism of chemotherapy resistance has become a common problem faced by clinicians and basic researchers. Professor Wang Hongxia led the team to start the exploration by analyzing the heterogeneity of the tumor microenvironment.
Professor Wang Hongxia introduced that in the tumor microenvironment, fibroblasts are the most numerous cell type and have been proven to play a key role in regulating tumor metastasis, angiogenesis and treatment. The research team used breast cancer tissue chips and clinical samples from patients receiving neoadjuvant therapy and found that the enrichment of a type of fibroblasts called TSPAN8+ myCAFs was significantly related to drug resistance and recurrence progression in breast cancer patients. In their study, they confirmed the important role of this fibroblast in chemotherapy resistance and poor prognosis. This means that the “culprit” of resistance to chemotherapy that has long plagued breast cancer patients has been found.
During the interview, the reporter learned that in the past, people believed that senescent cells were a group of cells that were about to die. Cellular senescence is considered a complex stress response and a barrier to tumorigenesis. However, the research team conducted relevant comparative experiments and found that for fibroblasts of TSPAN8+ myCAFs, cell senescence is a disguise. In order to further confirm the correlation and mechanism between aging characteristics and chemotherapy resistance, the research team used scientific and technological interference such as senescence antagonists and targeted knockout of key aging molecules and found that these "new subpopulations" of cells use senescence strategies to resist chemotherapy. etc. mechanism.
To further advance clinical diagnosis and treatment, the research team found ways to reverse cellular aging and chemotherapy resistance. Professor Wang Hongxia said that this discovery provides a new treatment strategy for the clinical reversal of chemotherapy resistance in breast cancer, especially triple-negative breast cancer. (over)