New agent disables survival proteins in recurrent blood cancers
Researchers have developed a prototype compound designed to hit protein targets that regulate cell death in hematologic cancers. The anticancer peptide, called stapled BIM BH3 peptide, overcomes the stubborn resistance to chemotherapy and radiation encountered when a blood cancer recurs following initial treatment.
The peptide suppressed cancer growth in mice with drug-resistant leukemia and showed synergistic anticancer activity when administered with other drugs, according to Loren Walensky, MD, PhD, of Dana-Farber/Children's Hospital Cancer Center in Boston, Massachusetts, and colleagues.
Many types of survival proteins are activated by cancers that recur. “It's as if relapsed cancers ‘learned' from their initial exposure to chemotherapy such that when they come back, they put up a variety of formidable barriers to apoptosis [programmed cell death],” explained Walensky in a statement issued by Dana-Farber Cancer Institute to announce his group's findings, which were published by The Journal of Clinical Investigation.
Next-generation compounds that can block a wider range of survival proteins than current drugs can without jeopardizing normal tissues are needed. To that end, Walensky's group engineered a peptide that contains the death-activating BH3 domain of BIM, an especially potent killer protein that is able to neutralize all survival proteins in the BCL-2 family. BCL-2 proteins regulate cell survival as well as apoptosis.
The stapled BIM BH3 peptide disables the survival proteins within a cancer cell while also activating the cell's pro-death BCL-2 proteins, causing the cell to self-destruct. Noncancerous cells and tissues were relatively unaffected by the treatment.