Stem Cells and Cancer


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Givol and Gal. Identifying cancer stem cells














Ventures that hold the most promise often present the greatest risk. Stem cells, for instance, with their talent for self-renewal and the potential to turn into any kind of cell, hold the promise of curing any number of diseases. But researchers have discovered in recent years that the risk of developing cancer is intimately tied to the promise of stem cells.

Adult stem cells, which are specific to each tissue type, function to maintain the body’s organs over the course of a lifetime, creating new cells to replace dead ones. Like their embryonic cousins, adult stem cells can renew themselves endlessly, and the process of differentiation, in which cells take on the characteristics of specific tissues, is inhibited. However, these exact properties make stem cells good candidates for turning cancerous. Recent theories propose that when an adult stem cell mutates, it can lose some of its properties of self-control while retaining its propensity for self-renewal – a dangerous combination that may lead to cancer.
In the past decade, scientists have discovered small amounts of stem cells, dubbed cancer stem cells, in many different types of cancer, including leukemia, breast cancer and brain tumors. These, they believe, are responsible for the continuous growth and post-treatment relapse of the cancer. Cancer stem cells are often especially resistant to standard chemotherapy drugs; they may survive treatment and eventually renew the cancer.
How, then, can cancer stem cells be targeted and destroyed? Recent research by Prof. David Givol and research student Hilah Gal of the Molecular Cell Biology Department, carried out together with Prof. Tsvee Lapidot of the Immunology Department and Prof. Eytan Domany of the Physics of Complex Systems Department, aimed to see what distinguishes cancer stem cells from other cancer cells and from healthy stem cells. Also participating in the research were Prof. Gideon Rechavi and his research team from the Sheba Medical Center, Tel Hashomer.
Upon comparing levels of gene expression in leukemia stem cells with those of non-stem leukemia cells, the scientists found about 400 genes that are expressed differently in the two types of cancer cell. In the cancer stem cells, for instance, certain genes involved in repairing mistakes in DNA were less active, possibly explaining the fact that these cells are more liable to accumulate harmful mutations. The team then compared the expression patterns of these 400 genes to those of healthy blood stem cells. About a third of them were common to both.
The trick now is to examine the patterns that distinguish the cancer stem cells from normal ones. If important patterns of activity that are unique to cancer stem cells can be identified, a way might be found to block these functions in the cancer stem cells without harming healthy adult stem cells. The team discovered that over half of the genes in cancer stem cells are expressed differently from those of adult stem cells, and these will hopefully provide a starting point in the search for promising drug targets. 
Prof. Eytan Domany’s research is supported by the Clore Center for Biological Physics; the Kahn Family Research Center for Systems Biology of the Human Cell; the Yad Abraham Research Center for Cancer Diagnostics and Therapy; the Ridgefield Foundation, New York, NY; the Wolfson Family Charitable Trust; and Mr. and Mrs. Mordechai Segal, Israel. Prof. Domany is the incumbent of the Henry J. Leir Professorial Chair.
Prof. Tsvee Lapidot’s research is supported by the Helen and Martin Kimmel Institute for Stem Cell Research; the Belle S. and Irving E. Meller Center for the Biology of Aging; the Gabrielle Rich Center for Transplantation Biology Research; the Crown Endowment Fund for Immunological Research; and the Charles and David Wolfson Charitable Trust. Prof. Lapidot is the incumbent of the Edith Arnoff Stein Professorial Chair in Stem Cell Research.