The Double Life of MCL-1

Myeloid leukemias cellular involvement of MCL1

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

(RxWiki News) Figuring out the molecular puzzles that can change a healthy cell to a cancer cell would be difficult even if you could watch the process happen.

Until that day comes, scientists must guess and then attempt to prove their theories.

For example, the protein MCL-1, which belongs to a family of surface molecules that prevent cellular death, was recently found to be intimately involved in an entirely different part of the cell, the mitochondria, where it is a key part of energy production.

"Ask your oncologist about sequencing your cancer."

With this information, researchers from the St. Jude Children's hospital feel that drugs targeting MCL-1 would be the ideal treatment for myeloid leukemias, as the protein is involved in both energy production and preventing normal mechanisms of cell death.

For these advantages, extra copies of this protein are frequent mutations for cancers.

Developing a drug should not prove too difficult, because similar proteins have already had drugs developed to target their structure.

With slight modifications, similar drugs could destroy the MCL-1 protein in the mitochondria, the powerplant of the cell, or possibly directly induce cancer cell death.

The drug would be a specific therapy, because cancer cells are a lot more dependent on these mitochondrial energy sources than normal cells, due to their rapid growth and high rate of metabolism.

The evidence from the lab results so far have backed up the theory. When targeted, destruction of the MCL-1 protein resulted in rapid and extensive cell death in cancers due to the double effect of increased vulnerability to cellular death as well as decreased energy production.

"We believe this newly identified form of MCL1 that works inside the mitochondria is probably essential for tumor cell survival. If that proves to be correct, then strategies to block the protein from getting into mitochondria offer a new therapeutic approach for cancer treatment," said Joseph Opferman, PhD and senior author of the paper.

The research was published April 29, 2012 in the journal Nature: Cell Biology.

Research was funded in part by the National Institutes of Health, the American Cancer Society, a National Cancer Institute Cancer Center Support Grant and ALSAC.

Reviewed by: 
Review Date: 
May 2, 2012
Last Updated:
May 14, 2012