Scientists estimate that triple negative breast cancer occurs in 15-20% of breast cancer cases. Patients with this form of the disease are missing three important therapeutic targets: estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2. Therefore, the majority of them are standard chemotherapy treatment rather than targeted drugs. Triple negative breast cancer (TNBC) most often affects young women, women of African descent and people with mutations in the BRCA1 gene.
The lack of highly efficient drugs in TNBC has prompted researchers to search for new drug targets and ways to destroy the path, cause the disease. They found two types of "weapons" - two drugs that have shown promising results in tests on mice.
"We may have found a way to treat resistant breast cancer, for which there is currently no targeted therapy by conversion of two older drugs (metformin and heme), already available on the market" - said the scientists from the University of Chicago.
None of these drugs has not been designed for the treatment of cancer. Metformin, which opened in 1922 and used in clinical practice since 1957, has been developed for the treatment of diabetes type 2. It reduces the production of glucose by the liver, and increases insulin sensitivity.
Although cancer is found more often in patients with diabetes than in healthy people, patients taking metformin have a lower risk of developing malignancies. The drug has a direct anticancer effect, which can inhibit the proliferation of tumor cells.
Another drug, gem, sold as pangematin, even older. It was first crystallized out of the blood in 1853. Currently, it is used in disorders of heme synthesis, which may cause the porphyrin disease. Many such patients receive pangematina injection obtained from the treated erythrocytes.
The researchers found that the primary target for anti-cancer heme is a transcription factor BACH1. This protein is often characterized by the increased expression at the triple negative breast cancer, it is essential for metastasis. BACH1 high levels are often associated with poor clinical outcomes. Fortunately, BACH1 can be inhibited with a small amount of side effects.
BACH1 sights on mitochondrial metabolism. He controls the rate of transcription of genetic information from DNA into messenger RNA by binding to specific DNA sequence. It can inhibit the transcription of a transport chain genes of mitochondrial electron energy key source cell. When BACH1 level is too high, the power is turned off.
"We found that we can deal with this problem with the help of protein BACH1 heme" - the researchers noted.
"When cancer cells are treated with hemin, BACH1 level decreases, which leads to a change in metabolic pathways of cancer cells. This leads to the fact that the cancer sensitive to metformin, inhibits mitochondrial respiration. We have found that a new combination, hemin and metformin, inhibits the growth of tumors in mice models "- the researchers reported.
"We believe that we can cover a number of different groups of patients with triple negative breast cancer, - added the scientists. - For example, patients with low and high expression BACH1 mitochondrial genes are likely to be responsive only to metformin. At the same time, patients with high and low BACH1 mitochondrial gene expression most likely will exhibit a resistance to metformin. However, addition of heme treatment will increase their sensitivity to metformin. "
The authors note that these results may help in the treatment of not only breast cancer. BACH1 expression is also observed in other cancers such as lung, kidney, uterus, prostate, and acute myeloid leukemia. BACH1-inhibiting genes mitochondrial electron transport chain appears to be a common mechanism.