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New
Therapeutic Target for Melanoma identified
Newswise — A protein called Mcl-1 plays a
critical role in melanoma cell resistance to
a form of apoptosis called anoikis,
according to research published this week in
Molecular Cancer Research.
The presence of Mcl-1 causes cell resistance
to anoikis.
This resistance to anoikis
enables the melanoma cells to metastasize
and survive at sites distant from the
primary tumor, according to Andrew Aplin,
Ph.D., an associate professor of Cancer
Biology at Jefferson Medical College of
Thomas Jefferson University, and a member of
the Kimmel Cancer Center at Jefferson.
The research was conducted at Albany Medical
College in New York by Dr. Aplin and
colleagues.
Mcl-1 is part of the Bcl-2 protein family,
and is regulated by B-RAF proteins, which
are mutated in approximately 60 percent of
all human melanomas.
The Bcl-2 family includes several
prosurvival proteins that are associated
with the resistance of cancer cells to
apoptosis, or cell death.
Dr. Aplin and colleagues analyzed three
candidate Bcl-2 proteins: Mcl-1, Bcl-2 and
Bcl-XL.
“When we depleted Mcl-1 from the tumor
cells, they were susceptible to cell death,”
Dr. Aplin said.
“Mcl-1 showed dramatic results compared to
Bcl-2 and Bcl-XL, which was a surprise. Our
findings show that targeting Mcl-1, which is
upregulated in a majority of melanoma cells,
could be a viable treatment strategy.”
Dr. Aplin said there are therapeutic agents
in development to target this protein
family, but most specifically target Bcl-2
and Bcl-XL.
There is one agent in development by Gemin X
Biotech that targets Mcl-1. This agent,
called obatoclax, is currently in phase I/II
trials.
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