New Drug Offers Hope for Chemotherapy-Resistant Blood Cancer Patients

Challenges in Treating Acute Myeloid Leukemia

Chemotherapy is a common treatment for acute myeloid leukemia (AML), a severe form of blood cancer that claims over 10,000 lives annually in North America. While chemotherapy can be effective, it fails in approximately one-third of patients, leading to a high mortality rate among those who do not respond to treatment. This situation underscores the urgent need for alternative therapies for blood cancer.

Research Insights from Canadian Scientists

Acute myeloid leukemia occurs when the bone marrow produces dysfunctional blood cells, undermining the body’s ability to transport oxygen and support the immune system. A Canadian research team has been investigating the bone marrow cells of patients resistant to chemotherapy, aiming to uncover the underlying reasons for their treatment challenges. Their recent findings, published in the journal *Cancer Discovery*, reveal a promising new drug that could enhance chemotherapy effectiveness.

Mechanism of Action: Inducing Cancer Cell Suicide

Many chemotherapy agents work by triggering apoptosis, or programmed cell death, in cancer cells. In their study, researchers focused on why this mechanism was ineffective in chemotherapy-resistant patients. They identified an overproduction of a protein known as MDM2 in the bone marrow cells, which inhibits the apoptosis pathway, allowing cancer cells to survive.

Potential of MDM2-Blocking Drugs

The researchers hypothesized that drugs designed to inhibit MDM2 could enhance the lethality of existing chemotherapy treatments. To evaluate this, they conducted experiments involving the injection of chemotherapy-resistant bone marrow cells into mice. While mice treated solely with daunorubicin, a standard chemotherapy drug, experienced limited survival, those receiving a combination of chemotherapy and an MDM2 inhibitor not only survived but also regained lost weight and showed signs of complete remission.

Future Directions: Clinical Trials on the Horizon

The success of the MDM2-blocking drug in mice presents a promising avenue for treating leukemia. However, further clinical trials are necessary to establish the safety and efficacy of this approach in humans. The research team is in the process of planning a clinical trial, hoping that their findings will lead to new treatment options that could significantly improve survival rates for patients battling blood cancer.

References

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