Researchers have identified formidable new compounds to eradicate leukemia. Acting by “deactivating” the mitochondria of cancerous cells, these are even more effective when combined with current chemotherapy treatments.
“Cut off the power” of cancer cells
The mitochondria are tiny structures inside cells that produce energy. Over time, they can deteriorate, and be destroyed by a cellular process called mitophagy, which the cancer can disrupt in order to extend the life of these power plants. If such an intervention allows it to proliferate, it might also lead to its downfall, without causing too much damage to the surrounding healthy cells.
In the context of work published in the journal Leukemiascientists from the universities of Texas and Rice studied the ability of eight compounds targeting weakened mitochondria and inducing mitophagy to destroy cancer cells leukemia.
« The fact that they induce mitophagy suggested that they might be particularly toxic to leukemic cells. “, details Natasha Kirienko, lead author of the study. ” Since six of these eight small-molecule compounds were found to be lethal to leukemia cells, we looked at closely related molecules as well as different combinations. »
First promising results
The team identified up to 30 similar molecules for each of them, and then tested their toxicity to leukemic cells, either alone or in combination with existing drugs. In tests performed on cell cultures, six eradicated acute myeloid leukemiathe most common form of the disease, among which five have also been shown to be effective once morest acute lymphoblastic leukemia and chronic myeloid leukemia.
Combined with existing chemotherapeutic compounds, the new compound PS127B has been shown to be much more effective than current treatments. Quantifying the effectiveness of the joint use of two compounds, its synergistic coefficient was 29 with doxorubicin and 13 with cytarabine (any figure above 10 being synonymous with synergy).
Other tests carried out on rodents, in which cancer cells from human leukemic patients had been implanted, showed that another compound, PS127E, was particularly effective in eradicating them, leaving the surrounding healthy cells largely unharmed. The team is currently pursuing animal testing to ensure the safety of the compounds and to establish the optimal dosages for more types of blood cancers, paving the way for clinical trials.
