Triple negative breast cancer, that is, estrogen receptor negative, progesterone receptor negative and auxin receptor negative, is the most difficult breast cancer to cure in the world. This kind of breast cancer accounts for 15% to 20% of all breast cancers. It has the characteristics of early onset age, high malignancy, high organ metastasis rate and low 5-year survival rate. Tnbc does not express hormone receptor and auxin receptor, and has no response to existing hormone or auxin inhibitors. Because there are no specific molecular markers, Linyi has no targeted drugs and targeted therapy.
The low differentiation of tnbc is considered to be a disease derived from stem cells. Ceng Yi's team has been engaged in adult stem cells and cancer research for a long time. Pluripotent stem cells expressing reproductive markers were identified in mouse mammary glands for the first time. On this basis, Ceng Yi and Shao Zhimin further studied the expression and function of prorc in breast cancer. Proc immunohistochemical staining in 570 cases of breast cancer showed that proc was highly expressed in tnbc. The high expression of proc accounts for about half of tnbc patients, and the prognosis is worse than that of low expression. The researchers also found that tnbc caused by genetic brca 1 gene mutation mainly exists in cases with low expression of proc.
These results show that tnbc with high expression of prorc is a new subclass of tnbc. Using the patient transplantation model, the researchers found that in this subgroup, proc positive cells are rich in cancer stem cells. Because proc is the surface molecule of cell membrane, the antibody drug designed for it can play its role without entering the cell, so proc is an ideal drug target.
The researchers also screened and prepared human monoclonal antibodies against prorc by phage display. In tnbc transplanted tumor model with high expression of prorc, the antibody can significantly inhibit the growth of mice tumor. Antibodies (targeting tumor stem cells) combined with chemotherapy drugs (killing other cancer cells) have a good tumor suppression effect.