Researchers from Huntsman Cancer Institute (HCI) at the University of Utah have developed a new drug that can potentially be used as a standalone or combination treatment against a common blood cancer.
The new drug, described in a paper published in the journal Leukemia, is capable of inhibiting and overriding the negative activity of the so-called Philadelphia chromosome, which is present in up to 30 percent of adults diagnosed with acute lymphoblastic leukemia (ALL).
"When you treat these leukemia cells with chemotherapy, you want DNA damage to accumulate so the cancer cells will die. But because the Philadelphia chromosome continually causes repair, these cells don't retain enough DNA damage to die," said Srividya Bhaskara, Ph.D., an assistant professor of radiation oncology at the University of Utah and lead author of the study, in a press release. "Essentially they resist any kind of drug you use on them. So we had to find a new way to overcome this DNA repair addiction."
For the new drug, the researchers first collaborated with a pharmaceutical company to develop a drug capable of inhibiting the proteins histone deacetylases (HDAC) 1 and 2. HDAC 1,2 is known to be directly involved in DNA repair. They then tested the new drug on patient samples and mice.
Interestingly, the researchers observed that the mouse models treated with the HDAC 1,2 inhibitor drug have 50 to 70 percent reduction in leukemia load. No apparent toxic side-effects were seen in mice. Additionally, the models did not get sick from the drug. The therapeutic benefit of the HDAC 1,2 inhibitor remained even if used as a standalone or in combination with a low concentration of doxorubicin.
The drug doxorubicin is one of the components of the chemotherapy cocktail regimen currently used for Philadelphia chromosome-positive ALL patients. This combination-drug regimen breaks down the central hub for DNA repair, while the HDAC 1,2 inhibitor drug reduces different repair protein functions.
With the promising results of the study, the researchers were encouraged to conduct human clinical trials.
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