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 Shafer
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 4/16/2009