The drug, called interferon alpha (IFNa), is used to
clean up microscopic tumor cells that may remain in the
body following surgery for the disease. It is the only
drug approved for this purpose
Researchers say that these findings underscore the
need to develop ways to make melanoma cells more
vulnerable to the drug, or to overcome the block
within the cells that prevents them from responding to
it.
The study showed that melanoma cells taken directly
from patients, as well as those grown in the
laboratory, respond poorly to IFNa, even when the drug
is given at very high doses, while immune cells
respond well to the same substance.
The study, led by researchers with the Ohio State
University Comprehensive Cancer Center, is published
in the journal Clinical Cancer Research.
“IFNa is effective in only 10 to 20 percent of
patients, but it's the best therapy available for
these patients, and no therapies on the horizon have
been proven any more effective,” says principal
investigator William E. Carson, III, professor of
surgery and a melanoma specialist at Ohio State's
James Cancer Hospital and Solove Research Institute.
“It is critical that we understand exactly how this
drug works and learn how to improve its
effectiveness.”
IFNa is an immune-system hormone made by the body
to help other immune cells recognize and destroy
developing tumors. As a drug, the substance is used to
treat melanoma and other cancers.
Formerly, it was thought that IFNa acted directly
on melanoma-tumor cells to stop their growth. But
earlier research by Carson's laboratory and others
suggested that the drug has a greater effect on the
immune system.
“The present study confirms that earlier work,”
says first author Gregory B. Lesinski, a research
assistant professor in the department of molecular
virology, immunology and medical genetics. “The new
findings are significant because they confirm that the
immune system, and not the tumor cell, is the primary
target of IFNa.
“We show for the first time that even normal
melanocytes are inherently less responsive to IFNa
compared to immune cells.” Melanocytes are the normal
cells that, when cancerous, cause melanoma.
“Some unknown factor in melanoma cells seems to
turn down their response to IFNa,” Lesinski explains.
“We are now trying to understand what that factor
might be.”
Funding from the Harry J. Lloyd Charitable Trust,
the National Cancer Institute, and The Valvano
Foundation for Cancer Research Award supported this
research.
