 The cancer stem cells (CSC) are those that
costain with the cell surface marker CD44
(green) in combination with a known stem
cell-related nuclear protein (red). Note that the
CSC population makes up a distinct layer of
cells, stained both red and green, within the
overall tumor cells. |
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Introducing the Ludwig Center
The Ludwig Center at Stanford University is at the forefront of an entirely new approach to cancer treatment that targets the rare cells at the root of some, and possibly all, cancers - cancer stem cells. Evidence continues to mount that these cells alone have the capacity to produce new tumor cells and spread the malignancy. Current treatments mainly seek to destroy the greatest number of cancer cells and shrink tumor size, yet without eradicating the most dangerous cells the tumor is likely to return. Investigators in the Ludwig Center have already isolated several cancer/leukemia stem cells, and are focused on isolating and characterizing cancer stem cells for each human cancer. By understanding the regulatory processes of these cells and the genetic mutations that cause them to act abnormally, the Center is working to identify novel imaging and therapeutic targets and develop life-saving treatments that eliminate cancer at its source. The Ludwig Center is a collaboration of Stanford's National Cancer Institute-designated Cancer Center and its Institute for Stem Cell Biology and Regenerative Medicine. Both the Cancer Center and Institute are led by Irving Weissman, MD, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research. Beverly Mitchell, MD, George E. Becker Professor of Medicine, serves as Deputy Director of the Cancer Center.  – Irving Weissman, MD, Director of the Ludwig Center The fundamental goal of the Ludwig Center at Stanford University is to build on pathbreaking work that sets the stage for understanding the role of normal stem cells in tissue regeneration and malignant stem cells in cancer. The Ludwig Center also is led Irving Weissman, MD. His laboratory was the first to identify and isolate normal blood-forming stem cells in mice and in humans – which led to the use of cancer-free blood stem cells in clinical trials – and the malignant counterparts of these cells in leukemia and other blood disorders. He is joined by Michael Clarke, MD, Deputy Director of the Ludwig Center, who identified the first cancer stem cell in a solid tumor. [Read the transcript of a question-and-answer session on stem cell research with Dr. Weissman, conducted by The Newshour with Jim Lehrer on PBS.] Since cancer stem cells appear to be the engines of metastasis, their identification, characterization and isolation are essential to the development of new therapeutics to prevent tumor growth and spread. A key characteristic of stem cells is their ability to self-renew uncontrollably. These cells are known to be at the root of several cancers and may be the cause of many more. While chemotherapy and other established cancer treatments destroy most cancer cells, they do not specifically eliminate the source of the cancer – the cancer stem cells. The goal of research at Stanford’s Ludwig Center is to develop therapies that target and eradicate these cells. This effort begins with identifying other cancer stem cells in solid tumors, characterizing those cells, learning the biological pathways allowing the cells to self-renew and then developing and testing new imaging diagnostics to chart tumor spread and to develop new therapies to target their destruction. Institute for Stem Cell Biology Stanford Cancer Center |
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Translational Research
Michael Clarke, MD (left), Deputy Director of the Ludwig Center and Karel H. and Avice N. Beekhuis Professor in Cancer Biology, and his team are applying their discoveries of cancer stem cells in human breast, colon, and head and neck tumors to improve patient diagnosis and treatment. The center image shows cancer stem cells with nuclear expression of a protein involved in stem cell self-renewal. The image on the far right is a non-tumorigenic colon cancer cell that does not contain the nuclear protein linked to self-renewal.
Collaborations are under way at Stanford to identify for the first time stem cells in a wide range of solid tumors, including brain, ovarian, head and neck, lung, bladder, prostate, skin, colon and breast cancers. These collaborations involve oncologists and investigators at the Stanford Cancer Center along with researchers in the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Characterizing cancer stem cells also draws on Stanford’s strengths in genomic analysis. Dr. Clarke has worked with Patrick Brown, MD, PhD, professor of biochemistry, to generate the most accurate predictive signature to date for patient outcomes based on expression analysis of breast cancer stem cells. This type of work in breast and other cancers will lead to diagnostics that help doctors predict disease severity so they can plan treatments accordingly. Based on similar data in colon cancer, collaboration is under way with surgeon Andrew Shelton, MD. By knowing in advance which tumors are likely to be less aggressive, Dr. Shelton hopes to spare many patients unnecessary colostomies. Each of the identified cancer stem cells will likely have characteristics of the tissue of origin and share features with other self-renewing stem cells. For a treatment to work, it must target those features that distinguish the cancer stem cells from surrounding tissues. Achieving that end involves understanding how certain pathways permit these cells to self-renew, which could provide targets for drug screening and preclinical testing led by the Cancer Center’s Beverly Mitchell, MD. Some of these distinguishing features should lead to the development of new imaging tools, also. Sam Gambhir, MD, PhD, Director of Stanford’s Molecular Imaging Program, has assembled a multidisciplinary team of radiologists, nuclear medicine experts and engineers to find ways to locate small nests of cancer stem cells in the body. The Ludwig Center will also incorporate research exploring ways to utilize the body’s own immune system to attack and destroy cancer stem cell proteins. Ron Levy, MD, the Robert K. and Helen K. Summy Professor in the School of Medicine, has been at the forefront of the longstanding effort to develop such therapies for cancer. Research building on Dr. Levy’s past efforts, as well as the work of Edgar Engleman, MD, in finding ways to stimulate immune responses to cancer, and that of Mark Davis, PhD, in developing techniques to isolate and use specific anti-cancer T cells, may lead to therapies that turn the immune system against cancer stem cells while sparing healthy tissue and normal tissue-specific stem cells. Together, these research programs have already opened a new frontier to our understanding of cancer, along with the possibility of interrupting the processes that cause it. Moving forward, researchers at the Ludwig Center, working in tandem with others in the field, will build on initial successes to ameliorate suffering and create life-saving treatments for cancer patients. |
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