City of Hope researchers have shown that an investigational drug already in clinical trials for blood disorders also stops the growth of many solid-tumor cells. The study, recently published in the journal Cancer Cell, suggests the drug potentially may work against a wide variety of cancers.
Beckman Research Institute researchers focused on a compound called AZD1480. The drug was designed to hinder a protein called Janus kinase 2, or JAK2.
|Michael Hedvat studies STAT3 in Richard Jove’s lab. (Photo by Darrin S. Joy)|
JAK2’s normal function in the cell is to activate certain other proteins. It also plays a role in several diseases involving abnormal blood cell growth, including some that can lead to blood cancers.
City of Hope investigators believed that AZD1480 might do even more.
Scientists know that Janus kinases like JAK2 can activate other important proteins called STATs, or signal transducers and activators of transcription. The STAT called STAT3 — when activated — can both promote cancerous tumor growth and shield cancer from the immune system.
Because activated STAT3 promotes cancer cell growth, researchers have been searching for drugs that can interfere with it.
The City of Hope researchers wanted to know if blocking JAK2 with AZD1480 would prevent activation of STAT3 — so they applied the drug to tumor cells with high levels of activated STAT3. Results were promising.
“When we added AZD1480 to the cells, we saw a big drop in the levels of activated STAT3,” said Michael Hedvat, a graduate student in the Irell & Manella Graduate School of Biological Sciences and the study’s lead author. The finding confirmed that JAK2 is key to activating STAT3, he said.
Senior author Richard Jove, Ph.D., Morgan and Helen Chu Director’s Chair, director of Beckman Research Institute and professor in the Department of Molecular Medicine, noted that STAT3 is a key protein in many cancers, making it a promising target for new anticancer drugs. “The connection between JAK2 and STAT3 now gives us more possible targets that we can develop drugs against,” he said.
Because AZD1480 is already in clinical studies for other diseases, the research team hopes to see it in clinical trials aimed at breast, prostate, colon and other solid-tumor cancers soon.
Other City of Hope researchers on the study include Anne Schroeder, Ralf Buettner, Ph.D., Claudia M. Kowolik, Ph.D., and Brian Armstrong, Ph.D., from the Department of Molecular Medicine, and Andreas Herrmann, Ph.D., Hong Xin, Ph.D., and Hua Yu, Ph.D., from the Department of Cancer Immunotherapeutics and Tumor Immunology.
AZD1480 was created by British pharmaceutical company AstraZeneca. The National Institutes of Health and AstraZeneca supported the study, which was published Dec. 8, 2009.