New research has identified a unique form of chemotherapy that preliminary experiments show is effective in targeting different leukemia cells.
Published in the journal Leukemia, a study by researchers at Rice University and the University of Texas MD Anderson Cancer Center has found new potential in various compounds that specifically target mitochondria, which provide energy to cells.
“While this is very promising, we are still a long way from having a new treatment that we can use in the clinic,” Rice biochemist Natasha Kirienko and corresponding author of the study said in a statement. “We still have a lot to discover.”
The researchers previously screened about 45,000 small-molecule compounds to find some that target mitochondria.
For their latest study, they chose eight and found between five and 30 close analogues for each.
The researchers then performed tens of thousands of tests to determine which were toxic to leukemic cells, either alone or in combination with existing chemotherapy drugs such as doxorubicin.
All eight compounds have previously been shown to target mitochondria by starting a process called mitophagy, or when a cell downgrades and recycles its old mitochondria.
Cancer is known to use mitophagy for nourishment, according to the researchers, with previous research showing that leukemia cells have much more damaged mitochondria than healthy ones.
Researchers thought that drugs that cause mitophagy might weaken leukemia cells and make them more sensitive to chemotherapy.
Ultimately, they found six were the most effective at killing acute myeloid leukemia cells. Of these, five were equally effective in killing acute lymphoblastic leukemia and chronic myelogenous leukemia cells.
All of the mitophagy-inducing drugs caused significantly less damage to healthy cells, the researchers found.
The experiments also showed that several mitophagy-inducing compounds were “significantly” more synergistic with doxorubicin.
For their latest experiments, the researchers tested one of the most effective compounds on mice implanted with cancer cells from a leukemia patient.
The study found that the compound was effective in killing acute myeloid leukemia cells in mice.
“We need to refine the dose that we think is best, and perhaps most importantly, we need to test on a wide variety of AML (acute myeloid leukemia) cancers,” Kirienko said.
“AML has many variations, and we need to know which patients are most likely to benefit from this treatment and which are not. Only after doing this work, which can take a few years, do we we can start testing in humans.”