HELSINKI: In addition to chemotherapy, targeted medications have been created to treat cancer. These medications only impact cancer cells, sparing normal cells. A novel targeted therapy for the treatment of acute myeloid leukaemia is called venetoclax (AML). In Finland, Venetoclax just received marketing authorization.
Venetoclax works by sensitising cancer cells to programmed cell death. However, a new study now shows that venetoclax does not appear to be effective against erythroid and megakaryoblastic leukaemias, two rare subtypes of the disease that are difficult to treat. In these leukaemia types, malignant cells resemble blood stem cells that produce red blood cells or platelets. Currently, few treatment options are available to these patients.
The study carried out by the University of Helsinki, HUS Comprehensive Cancer Center and the University of Copenhagen identified a new targeted drug, which may in the future offer a therapeutic option to patients with these subtypes of the disease. The study was published in the Blood journal in December.
In the laboratory, the researchers screened a wide selection of pharmaceutical agents that could be effective specifically against erythroid or megakaryoblastic leukaemia cells.
Among the more than 500 agents analysed, BCL-XL protein inhibitors in particular were effective in killing cancer cells isolated from these types of leukaemia. The BCL-XL protein has a similar function of preventing cells from being driven to programmed cell death as BCL-2, the target of venetoclax. At the moment, BCL-XL inhibitors are not used to treat patients, but their efficacy and safety are currently being investigated in clinical trials.
“The introduction of venetoclax has significantly improved the prognosis of AML patients. However, our research indicates that venetoclax is unlikely to function optimally against the subtypes of AML in our focus. Nevertheless, the finding should be verified in larger patient datasets,” says physician-scientist Olli Dufva.
AML is the most common type of acute leukaemia in adults. It can be divided into subtypes based on mutations and the degree of differentiation of leukaemia cells. One challenge associated with the use of targeted drugs is identifying patients who benefit from the new drug options. This study contributes to making the selection of targeted drugs more precise.
“The laboratory findings provide evidence that patients with erythroid or megakaryoblastic acute leukaemia would be a promising group for investigating the efficacy of BCL-XL inhibitors in clinical use,” says postdoctoral researcher Heikki Kuusanmaki.
The researchers believe that BCL-XL inhibitors will be trialled in the treatment of these leukaemia types in the near future.
“This finding may in the future improve the prognosis of these very rare and difficult-to-treat leukaemias,” says Professor of Translational Haematology Satu Mustjoki from the University of Helsinki and HUS Comprehensive Cancer Center.
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