New study highlights potential of mitochondria-targeted chemotherapies. Scientists have discovered promising new drugs that work in concert with other drugs to deliver a deadly one-two punch to leukemia. The researchers are from Rice University and the University of Texas MD Anderson Cancer Cente
Researchers have discovered potential new drugs that work in concert with other drugs to deliver a deadly one-two punch to leukemia.Scientists have discovered promising new drugs that work in concert with other drugs to deliver a deadly one-two punch to leukemia. The researchers are from Rice University and the University of Texas MD Anderson Cancer Center.
Kirienko’s lab had shown in prior work that the eight compounds targeted energy-producing machinery inside cells called mitochondria. Dozens to thousands of mitochondria are at work every minute in every living cell, and like all machines, they wear out with use. The eight compounds induce, the housekeeping routine cells use to decommission and recycle mitochondria that are past their prime.
“We hypothesized that if they activate mitophagy, they may be particularly toxic to leukemia cells,” said Kirienko, the corresponding author of the new study. “And indeed, we found that six of the eight small-molecule compounds were deadly to leukemia cells. We then wanted to study them more in depth. So we looked at closely related molecules, and we looked at combinations.”
For example, one currently prescribed drug combination for leukemia — doxorubicin and cytarabine — has a synergy coefficient of 13, Kirienko said. The team’s experiments showed several mitophagy-inducing compounds were significantly more synergistic with doxorubicin. The most synergistic, a compound called PS127B, had a coefficient of 29.
In their final experiments, the scientists tested one of the most effective mitochondria-targeting compounds, PS127E, using a cutting-edge technique called a model. In PDX, also referred to as a “mouse clinical trial,” mice are implanted with cancer cells from a leukemia patient. Once the cells grow, the mouse is exposed to a drug or combination of drugs as a closer-than-cells test of the treatment’s effect. PDX tests on one compound, PS127E, showed it was effective at killing AML cells in mice.
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