Photo by Kristin Gladney
New research published in Cell Reports has revealed biomarkers that may help predict which acute myeloid leukemia (AML) patients will respond to treatment with PU-H71.
This drug targets a tumor-enriched form of the protein Hsp90 called teHSP90, which is critical to the growth of cancer cells.
However, previous preclinical experiments showed that PU-H71 only kills some AML cells.
“We observed that only a subset of leukemia patient samples were sensitive to the drug,” said study author Monica Guzman, PhD, of Weill Cornell Medical College in New York, New York.
“We wanted to be able to identify which patients with leukemia would respond to this drug.”
So Dr Guzman and her colleagues focused on groups of proteins that function within signaling networks in leukemia cells.
The researchers found that 2 of these networks, JAK-STAT and PI3K-AKT, were important for leukemia cells to function. These signaling pathways are critical for the survival of AML cells, and they, in turn, are dependent on teHsp90.
The team treated AML cells with PU-H71 and found that cells with greater JAK-STAT and PI3K-AKT activity were killed by the drug. Cells with less active signaling networks did not respond to PU-H71.
“Higher activation of these networks makes the leukemia cells more dependent on Hsp90,” Dr Guzman said. “Since PU-H71 targets teHsp90, leukemia samples with these features are good targets for treatment with the drug.”
The next step for Dr Guzman’s team is to test their findings in patients. Ideally, the JAK-STAT and PI3K-AKT signaling pathways will serve as biomarkers for identifying patients whose leukemias will be sensitive to PU-H71.
“We are working on a tool that will quickly and easily identify patients whose cancers will respond to PU-H71,” Dr Guzman said. “We are really looking forward to seeing this in leukemic patients and being able to offer them a new treatment.”
