Cancer Stem Cell Research Program – Stanford Cancer …

Although cancer cell lines provide information about cancer biology, their adaptation to the in vitro environment often results in biological properties that differ in crucial ways from de novo cancer cells. Members of this Research Program have developed a novel mouse model system that reliably permits individual cancer cells isolated directly from patients tumors to be transplanted orthotopically to the same organ or tissue in immunodeficient mice; cells are assayed for the ability to form a new tumor. Members of the program have prospectively identified a minority population of cancer cells in epithelial and hematopoietic malignancies, called cancer stem or initiating cells. The cancer stem cells have the unique ability to drive the growth (through self-renewing cell divisions) and spread of a malignancy in the mouse model system. The prospective isolation of cancer stem cells enables critical regulatory processes of these cells to be studied directly. This should result in the discovery of new therapeutic targets that can be exploited to develop novel and more effective cancer treatments. The specific goals of the Program and how the expertise of the Program members will facilitate their achievement are listed below.

Goal 1. To investigate potential pathways critical for self renewal, spread and survival of normal and cancer stem cells.

Self-renewal is the critical process by which stem cells regenerate themselves. In the absence of cancer stem cell self-renewal, tumor growth would eventually cease. If we can identify differences in self-renewal pathways in normal and malignant stem cells, these differences could be exploited to eliminate cancer stem cells. Thus, understanding self-renewal pathways should lead to elucidation of new drug targets.

Goal 2. To develop new therapies directed against cancer stem cells.

One of the major goals of this Program is to translate significant advances in our knowledge of cancer stem cell biology gained from basic bench research to the bedside in innovative clinical trials. The discovery of cancer stem cells has implications for the diagnosis, prognosis and therapy of cancer. We envision unique clinical studies that will exploit all of these possibilities. This aim will be informed by the progress on previous aims as novel cancer stem cells are identified and it is determined what distinguishes them from their normal tissue counterparts. The isolation and characterization of cancer stem cells together with the xenograft models of human cancers will allow us to investigate potential novel therapies against these cells.

Michael Clarke, MD

Roeland Nusse, PhD

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Cancer Stem Cell Research Program - Stanford Cancer ...