Chemotherapy does not work in some patients with blood cancer. A recent study has identified a new type of drug that could help.
Acute myeloid leukemia is a type of blood cancer that kills more than 10,000 people every year in North America. Chemotherapy can often successfully treat this disease, but it still fails in a third of patients. The majority of these chemotherapy-resistant patients will not survive. Because of this high failure rate, there is a need for new treatments for blood cancer.
Detective work in the clinic and the lab
Our bodies rely on blood cells to help our immune system and to transport oxygen from our lungs to the organs where it is needed. These blood cells are normally made in the bone marrow. Acute myeloid leukemia starts when the bone marrow starts to make blood cells that don’t work properly.
A Canadian research team has been studying bone marrow cells from chemotherapy-resistant patients, hoping to identify why their particular blood cancer is so hard to treat. They have recently identified a new drug that could make chemotherapy more effective. They published their results in the journal Cancer Discovery.
How to make cancer cells kill themselves
Many chemotherapy drugs work by convincing cancer cells to commit suicide. The researchers tried to track down why this wasn’t happening in these chemotherapy-resistant patients. They traced the problem to one protein that was being over-produced in their bone marrow cells. This protein, MDM2, blocks the suicide pathway, preventing the blood cancer cells from killing themselves.
A drug that blocks MDM2 can help chemotherapy drugs work
The researchers theorized that drugs which block MDM2 activity could help chemotherapy drugs kill blood cancer cells. To test this, they took bone marrow cells from chemotherapy-resistant blood cancer patients and injected these into mice. These mice go on to develop leukemia, lose weight, and then die.
Mice that received daunorubicin, a normal chemotherapeutic drug, lived a bit longer than mice without any treatment, but still died. However, all the mice given the combination of chemotherapy and an MDM2-blocking drug survived. In fact, these mice eventually gained back the weight they had lost after developing leukemia and appeared to have gone into complete remission.
The next step: a clinical trial with patients
Being able to save 100% of mice with leukemia is extremely encouraging. However, clinical trials are needed to show that MDM2-blockers are safe and effective in humans. The researchers are now planning a clinical trial, and hope that this study will eventually lead to a treatment that could save the lives of thousands of patients with blood cancer.
Written by Bryan Hughes, PhD
- Maganti, H. B., Jrade, H., Cafariello, C., Manias Rothberg, J. L., Porter, C. J., Yockell-Lelièvre, J., Battaion, H. L., Khan, S. T., Howard, J. P., Li, Y., Grzybowski, A. T., Sabri, E., Ruthenburg, A. J., Dilworth, F. J., Perkins, T. J., Sabloff, M., Ito, C. Y. & Stanford, W. L. Targeting the MTF2-MDM2 axis sensitizes refractory acute myeloid leukemia to chemotherapy. Cancer Discovery (2018) http://dx.doi.org/10.1158/2159-8290.CD-17-0841
- New drug combination destroys chemo-resistant blood cancer. 2018. The Ottawa Hospital. Accessed October 2018 at http://www.ohri.ca/newsroom/story/view/1054?l=en