If Michael Clarke is right, it may not be necessary to destroy every malignant cell to cure cancer. Killing just five percent of cells in the tumor may be sufficient. The trick, of course, is finding the right five percent.

Working with U-M scientist Sean Morrison and Max Wicha, M.D., director of the U-M Comprehensive Cancer Center and a professor of internal medicine in the Medical School, Clarke recently discovered that, just like every organ in the human body, the growth of cancerous tumors is regulated by stem cells. “One population of stem cells in cancer is responsible for its uncontrolled growth,” he says. “Current cancer therapies are only minimally effective, because the stem cells just keep making more tumor.”

Muhammad Al-Hajj, Ph.D., a post-doctoral research fellow in Clarke’s laboratory, spent the last two years sifting through hundreds of protein markers on the surface of cells from human breast tumors. “When we found cells with a marker that was common to tumors from most patients,” Al-Hajj says, “we isolated those cells and injected them into mice. Up to five percent of cells from human tumors also produced tumors in mice. These cells are capable of unlimited proliferation; the others divide up to a point and then die.”

Muhammad Al-Hajj Photo: Marcia Ledford

Clarke and Al-Hajj now are completing DNA analysis on breast tumor cells to identify which genes are active in cancer stem cells, but inactive in other cells from the same tumor.

The University of Michigan has filed a patent on Clarke’s discovery of stem cells in cancer. Clarke, Morrison and Wicha have established a new company called Cancer Stem Cell Genomics (CSCG) to develop and test new therapies to destroy or disable cancer stem cells.

In related work, Clarke identified recently a key gene involved in self-renewal of hema-topoietic stem cells. Morrison is analyzing the neural crest stem cells he studies to see if the same gene is responsible for their ability to make copies of themselves. Since uncontrolled growth is the essence of cancer, Clarke hopes his work with hematopoietic stem cells may help identify genes and proteins that would be good targets for future cancer therapies.

“I’m optimistic, because before this we couldn’t see the cancer cells we were trying to kill,” Clarke says. “Now we can at least identify the cells and see the target. It gives us a much better shot at a cure than we’ve ever had before.”

Also:

Sean Morrison

Michael Long

Marie Csete

Sue O’Shea

Richard Mortensen

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