New Therapeutic Target for Melanoma Identified
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.
Media Only Contact:Emily ShaferThomas Jefferson University Hospital
Phone: 215-955-6300
Published: 4-16-2009