Drug synergy: one step closer to effective treatment of acute myeloid leukemia

By James Bowers | PhD in Molecular Biology, Science Presenter, TV Researcher and Science Journalist

By combing two pre-existing therapies, researchers at the LBMCC/SNU dramatically increased their efficiency against leukemia cancer cells in certain patients.   

LBMCC proposes a new drug combination that could one day replace chemotherapy in leukemia patients who have a particular gene mutation. Photo credit: Pixabay.com

 

Analysis of existing drug molecules by the LBMCC lab may help pave the way for future cancer treatments. 

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Even though it remains a rare cancer type, estimations suggest 20,000 patients will be diagnosed this year in the USA alone. Years of research has led to a better understanding of this debilitating disease, which causes an overproduction of white blood cells in bone marrow, but the survival rate remains low.

Patients with AML are currently treated with chemotherapy in the hopes of pushing cancer into remission. If unsuccessful, the only real options are either more chemotherapy or a stem cell transplant. Prof. Marc Diederich and Dr Claudia Cerella’s collaborative research in Luxembourg, France and Korea has led to new ways to treat AML, and their most recent findings will be published in the prestigious journal, Leukemia. The team is analysing the anticancer potential of UNBS1450, a drug belonging to the group of cardiac glycosides, already prescribed for congestive heart diseases.

 

Targeting genes that control cancer cell death.

Several years ago research at LBMCC discovered that UNBS1450 switches off MCL1 expression, an essential gene involved in cancer cell survival. Considered one of the great hopes for the future of AML treatment, UNBS1450 is effective against MCL1 even at low doses. This approach, unlike traditional chemotherapy, has the potential to target only affected cells and leave the healthy ones alone, paving the way towards a more personalized treatment.

In brief, cancer cells are so dangerous because genes like MCL1 are continuously activated leading to the survival of unhealthy cells, which cluster into tumours or in the case of leukemia accumulate without physiological function. Previous research into UNBS1450 showed that it blocks the MCL1 protein, forcing the affected cells to self-destruct potentially reducing the tumour or number of leukemic cells. However, about a third of cancer patients also have a mutation in another gene, BCL2, which acts in a similar way to MCL1.

 

The LBMCC team studied the effect of targeting both cancer proteins at once. They used UNBS1450 combined with another innovative medication, Venetoclax. Treating cancer cell lines with both molecules was highly effective at inducing cell death in patients producing both cancer proteins. Better still, in leukemia cells taken from patients, the combined effect of the two treatments was better than either of them on their own and didn’t damage healthy cells nearby from patients. Importantly lymphocytes, that are essential to protect our body against infections, are not killed by the compound combination. Accordingly, this innovative combined targeted therapy should limit unfortunate side effects observed in AML patients undergoing chemotherapy. Findings such as these will help bring UNBS1450 into future clinical trials and pave the way for its use in combination with other drugs to treat AML.

 

This article was written by James Bowers. Follow him on Twitter: @jimbologist  

   

Drug synergy: one step closer to effective treatment of acute myeloid leukemia

Drug synergy: one step closer to effective treatment of acute myeloid leukemia

By combing two pre-existing therapies, researchers at the LBMCC/SNU dramatically increased their efficiency against leukemia...
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