A small-molecule compound that has previously shown activity against Ewing sarcoma and prostate cancer may fight leukemia as well, according to preclinical research published in Oncotarget.
The compound, YK-4-279, inhibits the oncogenic activity of the fusion protein EWS-FLI1.
“EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma,” said study author Aykut Üren, MD, of Georgetown University Medical Center in Washington, DC.
“It also appears to drive cancer cell growth in some prostate cancers.”
ETS family fusion proteins are found in patients with acute myeloid leukemia and acute lymphoblastic leukemia as well.
So Dr Üren and his colleagues decided to create a mouse model of EWS-FLI1-induced leukemia and assess the activity of YK-4-279 in this model.
Mice with EWS-FLI1-induced leukemia presented with severe hepatomegaly, splenomegaly, and anemia, followed by rapid death.
The investigators treated these mice with injections of YK-4-279 five days a week for 2 weeks or vehicle intraperitoneal injections on the same schedule.
The team said treatment with YK-4-279 significantly reduced white blood cell counts, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly.
They noted that mice experienced reductions in the weight of their spleens and livers without experiencing reductions in total body weight.
In addition, mice that received YK-4-279 had significantly better overall survival than control mice. The median survival times were 60.5 days and 21 days, respectively.
The investigators also noted that treated mice did not exhibit overt toxicity in the liver, spleen, or bone marrow.
“The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can’t be answered until we conduct clinical trials,” Dr Üren said.
Nevertheless, he and his colleagues believe these results support the continued preclinical development of YK-4-279 for Ewing sarcoma, prostate cancers, and leukemias with highly homologous translocation products or with a clear ETS-driven gene signature.
