Building on years of research showing that growth hormone receptor antagonist therapy can curb the growth of solid tumors such as prostate, breast and brain cancers, researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have turned their attention to acute myeloid leukemia.
The growth hormone-releasing hormone (GHRH) antagonist MIA-602 drastically reduced tumor growth in mice engrafted with human acute myeloid leukemia (AML) cells, according to a study published online April 16 in the British Journal of Haematology. In addition, the investigators confirmed expression of the GHRH receptor in nine of nine samples from patients with AML.
“This is the first demonstration that the GHRH antagonists, which I started developing some 20 years ago, are active against hematologic tumors,” said Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c., Nobel Laureate and Distinguished Leonard M. Miller Professor of Pathology and Professor of Hematology/Oncology at the Miller School.
Schally and colleagues previously showed that synthetic antagonistic analogues of GHRH suppressed the growth of 60 different human cancer cell lines that represent more than 20 types of cancer. However, this treatment strategy was never before assessed in leukemia.
The findings offer a potential new therapeutic pathway for treating AML, the researchers noted.
“This opens the door for more personalized medicine,” said lead study author Joaquin J. Jimenez, M.D., a research professor in the Department of Dermatology & Cutaneous Surgery and the Department of Biochemistry & Molecular Biology at the Miller School.
The GHRH antagonist in development “is a new avenue for patients who might not respond or stop responding to conventional therapy, or it could be used in combination with conventional therapy,” he added.
Interestingly, the therapy only works with cancer cells that feature GHRH receptors. Otherwise, the MIA-602 antagonist has nothing to attach to in order to suppress cancerous cell growth. These receptors were present on three out of four leukemic cell lines tested in the study, for example.
“If the patient’s leukemic cells do not have the receptors, there is no use in treating them this way,” Jimenez said.
GHRH occurs naturally in humans. The hypothalamus releases GHRH to signal the pituitary gland, in turn, to release growth hormone. However, cancer cells can also produce GHRH where it can signal nearby tumor cells to grow uncontrollably.
In receptor positive patients, this strategy could also help doctors monitor response to treatment over time, Jimenez added.
“Without the collaboration and support at Sylvester there is no way we could do something like this,” he said.
Schally, Jimenez and their colleagues plan to continue researching this antagonist in development. “We’re also trying to improve the therapies,” Schally said. “One way is to develop more powerful antagonists that can be used at lower doses.”
Buoyed by their initial success in the current study, the researchers plan to investigate the potential efficacy of MIA-602 in other hematologic malignancies. Schally added, ““Work in oncology is never done.”