Research shows cell’s inactive state is critical for effectiveness of cancer treatment

by Esther Napolitano, napolite@mskcc.org
Memorial Sloan-Kettering Cancer Center

A new study sheds light on a little understood biological process called quiescence, which enables blood-forming stem cells to exist in a dormant or inactive state in which they are not growing or dividing. According to the study’s findings, researchers identified the genetic pathway used to maintain a cell’s quiescence, a state that allows bone marrow cells to escape the lethal effects of standard cancer treatments.

Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) found elevated levels of the tumor suppressor protein p53 in hematopoietic stem cells (HSCs) immature cells in the bone marrow that have the capacity to differentiate into all types of mature blood cells. They showed that when chemotherapy or radiation is delivered to a cell that lacks both p53 and a gene called MEF, the cell not only becomes less quiescent, but also becomes more susceptible to being killed. These findings are published in the January 9, 2009, issue of Cell Stem Cell.

“This is the first time that anyone has established that p53 has a role in defining a cell’s state of quiescence. Furthermore, it is surprising that some cells that lose p53 can actually be killed more readily than those that have p53 intact,” said the study’s senior author, Stephen Nimer, MD, Chief of the Hematology Service and Member of the Molecular Pharmacology and Chemistry Program at MSKCC. “Our findings have important implications for developing therapeutic strategies that could eliminate quiescent cancer stem cells.”

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