Treatment for leukemia may become more successful.
A new approach to the treatment for blood cancer and other types for cancer increases the patients’s chances of defeating the disease. Based on the results of a recent study, the treatment for leukemia will become more effective.
The discovery of a potentially new combination therapy for leukemia was made by the Australian Institute for Medical Research Walter and Eliza Hall.
Researchers at WEHI have discovered why some leukemia cells are resistant to new SMAC mimetic anti-cancer agents. This discovery could significantly improve the use of these medications in the
treatment for blood cancer.
This occurs before the expected effect of the used medication. Treatment for AML cells with MDR1 inhibitors allows SMAC mimetics to accumulate and kill leukemic cells. These researchers offer a new approach to understand which AML patients will respond best to SMAC mimetics. Also, on this basis, it becomes possible to use SMAC mimetics and combinatorially. This is a new combination therapy for leukemia or other cancers.
The study was supported by over US $ 80,000. Funds were received from over 400 financial donors.
The research report was published in the journal “Blood Advances”. A team of scientists led by Dr. Gabriela Brumatti, Dr. Emma Morrish and Prof. John Silke of WEHI worked in collaboration with researchers from Monash University, the University of Adelaide and the Peter McCallum Cancer Center.

Medication resistance is a major obstacle to a successful treatment.

The main challenge facing researchers is to overcome the medication resistance of cancer cells.
SMAC mimetics represent a new class of anti-cancer agents. All of them have undergone clinical trials for the treatment for some complex oncological types, including blood cancer. Dr. Brumatti said that these agents unfortunately did not work with many types of cancer.
“Many teams, including our, have now begun to research a very important issue. Could SMAC mimetics be more effective when it´s combined with other anti-cancer agents” she continued. “We decided to conduct a systematic search for new medications that can improve the response of leukemia cells to SMAC mimetics. We have tested nearly 6,000 medication-like inhibitors of various cellular proteins.

“Our research focused on AML, an aggressive form of blood cancer. This type of cancer has a very negative outlook for many patients. It is necessary to develop more effective methods of treatment
as soon as possible.”
This search for “needles in a haystack” eventually yielded several candidates for these medications.
One of them was the MDR1 inhibitor, as reported by Dr. Morrisch.

“MDR1 is a protein found in healthy body cells. But its level can be increased in some cancers. This protein pumps out certain molecules from cells. In nature, it protects healthy cells from the
accumulation of toxins. However, in cancer cells, MDR1 can have a negative effect. By pumping medications out of the cell, MDR1 stops the work of the used medications. Thus, the ongoing
treatment for leukemia becomes significantly less effective. The blood cancer itself is becoming very resistant to the medications which are necessary to use in the treatment” said Dr. Morrish.

What do scientists say about the research?

“We hypothesized that MDR1 could remove SMAC mimetics from AML cells. In our research, we found out that can be the case. The good news is that medications that inhibit MDR1 are already undergoing clinical trials. When testing these medications in combination with the help of SMAC mimetics, we saw that the AML cells retained the SMAC mimetics and began to die. “
“All of this suggests that MDR1 inhibitors can potentially be combined with SMAC mimetics to create a new effective combination therapy. It is significant that we already know from the results of previous clinical trials that both medications are good tolerated. Based on this, we hope that this combination of medications can be not only safe, but also very effective.
Dr. Brumatti believes that a significant aspect of the study was that the combination of MDR1 inhibitors and SMAC mimetics could also kill leukemia stem cells. We are talking about precisely those cells that are considered to be the cause of cancer recurrence. “This discovery is really
extremely important! It demonstrates that the developed medical combination can provide
sustainable positive dynamics for patients. In addition, this therapy reduces the risk of recurrence” she said.