A drug that singles out and starves cancer cells is entering clinical trials for the treatment of acute myeloid leukemia.

Patients with acute myeloid leukemia have bone marrow that creates abnormal blood cells, which can overcrowd normal necessary blood cells. Current treatment methods, which involve chemotherapy and other drug combinations, result in survival rates of 40 percent for patients under the age of 60 and rates as low as 5 to 10 percent for patients over 60. 

In response to low survival rates for acute myeloid leukemia and other cancers, UT’s MD Anderson Cancer Center introduced its Cancer Moon Shots Program in 2012 to develop better methods of treatment. Scientists in MD Anderson’s Institute for Applied Cancer Science, which is part of the Cancer Moon Shots Program, recently developed the drug IACS-10759 to target tumor metabolism in patients with acute myeloid leukemia.

Normal cells have two ways of producing energy, but some tumor cells can only use oxidative phosphorylation, a process which involves the transfer of electrons between molecules. The IACS-10759 drug targets mitochondria inside tumor cells, inhibiting oxidative phosphorylation and effectively starving tumors.

Marina Konopleva, professor of leukemia at MD Anderson and head of clinical trials for the drug, said that scientists developed this new tumor drug after realizing the leukemia cells rely on oxidative phosphorylation. 

“We found that leukemia cell lines in patient samples or mice injected with human leukemia cells are sensitive to this particular drug,” Konopleva said.

The team received approval from the Food and Drug Administration to begin phase I clinical trials for the drug in 2017. Phase I clinical trials will include testing safety and finding an acceptable dosage range. Around thirty patients with resistant or relapsed acute myeloid leukemia will participate in Phase I. An additional ten to twelve patients will join later in the trial.

Development relied on expertise from a multidisciplinary team, including scientists in medicinal chemistry, biology and pharmacology, said Maria Emilia di Francesco, associate director of medicinal chemistry at MD Anderson and leader of the drug’s development.

“Each time there is a new biological hypothesis, it really takes an army of scientists to demonstrate that this hypothesis has some clinical applications,” di Francesco said. “If you think about a biological target involved — if you inhibit the target — you deeply affect cancer maintenance.”

The Institute is also studying models of how the drug treats other solid tumors, di Francesco said. 

From conception to the beginning of clinical trials, the process of developing the new drug will have taken five years, which is considerably shorter than the ten years drugs typically take to reach clinical trials in industry, Konopleva said. 

“This exemplifies that drug development can be done within academia perhaps faster and more successfully,” Konopleva said. “We joined forces with people very experienced in drug development — academic investigators plus clinical investigators … By working all together, we can bring new treatments to patients much faster than through regular processes.”