Breast Cancer

The problem

Triple negative breast cancer is a dangerous medical condition. The cells that cause these tumors do not contain three proteins and so they do not respond to customized and powerful cancer treatments. That is why, doctors are forced to use chemotherapy for treatment of patients suffering from this medical condition. The problem is that chemotherapy medicines offer long-term effectiveness only in 20% of women who suffer from triple negative breast cancer.

The new solution

Researchers at The Johns Hopkins University recently discovered the process through which the breast cancer cells resist the effects of chemotherapy. And once this is known, they have also found a method to reverse the process. The findings were published in the journal Proceedings of the National Academy of Sciences.

Triple negative breast cancer

Triple negative breast cancer amounts to about 20% of the all breast cancers. It also consists about 30% of the breast cancers in African-American women. The cells responsible for the cancer are resistant to chemotherapy. Besides, they also have a large number of breast cancer stem cells. These are the cells which are responsible for relapses and they also cause production of metastatic tumors ultimately leading to the death of the patients.

The study

A research team directed by Gregg Semenza, M.D., Ph.D., decided to study about the cancer tied and tried to see if HIF inhibitors were able to improve the effectiveness of chemotherapy. The study found that chemotherapy turns on HIF, which improves the survival of breast cancer stem cells. These are the cells which are responsible for the relapse and metastasis and they should be killed to save the patient. There are medicines available that can block HIF and thereby stop the circle.

The study treated lab grown triple negative breast cancer cells using the chemotherapy drug paclitaxel. The researchers look for the changes in HIF levels. After a few days HIF protein and activity levels increased and along with that the percentage of breast cancer stem cells also increased. When the cancer cells were genetically altered to have less HIF, chemotherapy could destroy the cancer stem cells. It meant HIF was necessary for the cancer stem cells to avoid the effects of the chemotherapy drug.

HIF increases the survival of the stem cells by increasing multidrug resistance protein 1 (MDR1), a protein. This protein works like a pump and expels chemotherapy medicine from cancer cells. When the chemotherapy drug was administered along with the HIF inhibitor digoxin, MDR1 levels went down.

The study done on mice found that if treatment is done with digoxin and paclitaxel, the tumor size reduced by 30% compared to the treatment done using only paclitaxel. Besides reducing the levels of MDR1, the combination treatment also reduces the number of breast cancer stem cells. When digoxin and another chemotherapy drug gemcitabine was combined in a treatment, the tumor volumes came down to 0 within three weeks. It also revealed that the relapse that was generally seen after the completion of the treatment.

Patient database analyses also revealed that women who were suffering from triple negative breast cancer and were treated with chemotherapy showed different death rates. Patients with higher than average HIF activities in the tumors had higher risk of dying of breast cancer than patients with lower than average HIF levels.  HIF inhibitor digoxin is already approved by the FDA for treatment of heart failure. Scientists have already identified several other drugs switch work as HIF inhibitors and they’re currently being tested for their capacity to help in the treatment of cancer. Positive clinical trial results will ensure that triple negative breast cancer patients will have more effective therapies soon.