Targeting Leukemia's Kill Switch

Leukemia treatment with selective BCL2 inhibitors overcomes cancer resistance

/ Author:  / Reviewed by: Robert Carlson, M.D

(RxWiki News) Once a resistance to chemotherapy develops in leukemia, it can be extremely difficult to turn back the tide. A new drug focuses on changing that.

Early studies in mice with transplanted human leukemias showed success in using a combination of two proteins that have the remarkable effect of triggering a suicide code, but only for cancer cells.

In simpler terms, there's a kill switch on cancer cells. But discovering it is a lot more complicated than it was in theory.

"Ask your oncologist about new research developments. "

Loren Walensky, MD/PhD, was the senior author of the study from the Dana-Farber Children's Hospital Cancer Center. Dr. Walensky states says that the most promising area of this research shows that using this drug, a fusion between the BIM and BH3 proteins, could take away the developed resistance of the leukemia to the previous chemotherapy drugs.

Molecular biologists have tried to target the apoptotic death domain using a family of proteins called BCL-2.

Several proteins and molecules are made by cancers to act as shields. The term best used in scientific literature to describe the effect of the various self-protective mechanisms in cancer cells is a force field. 

What the fusion of BIM and BH3 does is find a clever shortcut to the BCL-2 kill switch by focusing on a target nearby, and this begins a chain reaction that consumes the cell.

"The diversity of BCL-2 family survival proteins blunts the anti-tumor activity of essentially all cancer treatments to some degree," Dr. Walensky stated.

"By using Nature's solution to broad targeting of the BCL-2 pathway with a stapled BIM BH3 peptide, our goal is to eliminate cancer's protective force field and enable the arsenal of cancer treatments to do their job."

An editorial published alongside the research paper agreed with the conclusions of Dr. Walensky. Jerry M. Adams, PhD, found that the study showed promise, with no serious side effects observed in healthy blood cells during treatment.

Adams also agreed that the drug, by fusing the BH3 peptide to the BIM protein, was quite effective in killing the resistant leukemia cells by targeting the survival protein using BH3.

"The peptide killed cultured hematologic tumor cells and abated growth of a leukemia xenograft, without perturbing the hematopoietic compartment. Hence, such peptides might eventually provide a new way to treat refractory leukemias," Adams concluded.

As this research was performed on mice, clinical testing of the BIM-BH3 peptide has not yet been discussed.

The research was posted online in the Journal of Clinical Investigation on May 24, 2012.

Researchers disclosed financial ties with the manufacturer, Aileron Therapeutics.

Reviewed by: 
Review Date: 
June 7, 2012
Last Updated:
November 8, 2012