Exploiting estrogen receptor beta and TP53 interaction as a new therapeutic strategy for cancer
To induce cancer cell death, cancer cells are selected that express estrogen-receptor β (ERβ) and mutant tumor protein 53 (TP53). An agent that increases ERβ protein expression is administered to the cells to induce cell death. To treat a subject having a cancer that is characterized by cancer cells expressing ERβ and mutant TP53, an agent that increases ERβ protein expression is administered to induce cell death in the cancer cells. To increase estrogen receptor β (ERβ) expression levels in a subject having low ERβ expression levels, tamoxifen is administered to increase ERβ protein levels in the subject. To treat a subject having cancer cells expressing estrogen-receptor β (ERβ) and wildtype tumor protein 53 (TP53), an agent that inhibits ERβ and TP53 binding interaction is administered to induce cell death in the cancer cells of the subject.
1 . A method of treating cancer, the method comprising:
selecting a subject having cancer, wherein the cancer is composed of cancer cells expressing estrogen-receptor β (ERβ) and mutant tumor protein 53 (TP53) and not expressing estrogen-receptor α (ERα); and
administering an agent to the selected subject that increases ERB protein expression in the cancer cells, wherein the agent is tamoxifen or a tamoxifen metabolite; and administering at least one drug, sequentially or simultaneously, to the subject, in synergistic combination with the agent, wherein the drug is doxorubicin or carboplatin, wherein the agent and the drug are in amount effective to induce killing of the cancer cells of the subject.
2 . The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, triple-negative breast cancer, lung cancer, ovarian cancer, glioma, and colon cancer, and combinations thereof.
3 . The method of claim 1 , wherein the increase in ERB protein expression is any detectable amplification of the ERB protein level after the agent is administered to the subject.
4 . The method of claim 1 , wherein the subject is a cancer patient.
5 . The method of claim 4 , wherein the selecting step is a stratification of the cancer cells compared to a control and/or clinical guidelines.
6 . The method of claim 1 , wherein the tamoxifen metabolite is endoxifen.