BOSTON--Scientists at the Dana-Farber/Children's Hospital Cancer Center have developed an anti-cancer peptide that overcomes the stubborn resistance to chemotherapy and radiation often encountered in certain blood cancers when the disease recurs following initial treatment.
The strategy could pave the way for much needed new therapies to treat relapsed and refractory blood cancers, which are difficult to cure because their cells deploy strong protein "deflector shields" to neutralize the cell death signals that chemotherapy agents used against them initially, say the researchers.
The prototype compound, called a "stapled BIM BH3 peptide," is designed to disable the cancer's defenses by hitting a family of protein targets that regulate cell death.
In proof-of-concept studies in mice with transplanted, drug-resistant leukemia tumors, the compound alone suppressed cancer growth, and when paired with other drugs, showed synergistic anti-cancer activity, say researchers led by Loren Walensky, MD, PhD, of Dana-Farber/Children's Hospital Cancer Center.
Their paper has been posted online by the Journal of Clinical Investigation and will appear in the journal's June issue. Walensky is the senior author and James LaBelle, MD, PhD, is the first author.
A cell's "fate" when and whether it lives or dies depends on a tug-of-war between pro-death and anti-death forces within the cell that serve as a check-and-balance system to maintain orderly growth. The system is regulated by the BCL-2 family of proteins, which contains both pro-death and pro-survival members.
When cells are no longer needed or are damaged beyond repair, the body activates pro-death BCL-2 proteins to shut down mitochondria the power plants of the cell resulting in an orchestrated cellular destruction known as apoptosis, or programmed cell death.
Many cell-killing cancer treatments work by triggering these "executioner proteins" t
|Contact: Bill Schaller|
Dana-Farber Cancer Institute