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Targeting cancer at its roots

Glioblastoma is the most aggressive type of brain cancer and derives from cells that support the neurons in the brain. These tumors are usually rapidly growing and have access to an extensive blood supply, which helps them to further grow and to invade other areas of the brain. With the highest malignant grade comes also the highest risk for recurrence. Current therapy for this type of tumor includes surgery followed by combined chemo- and radiation therapy. This therapy has significantly increased the overall survival of patients but many of these tumors ultimately recur.

One focus of our research is to target a small population of cells within the tumor known as cancer stem cells or tumor initiating cells. Recent experimental data suggests that these cells may actually be the driving force of the tumor and may be responsible for the invasion of the tumor into normal brain, making complete surgical resection difficult. The cancer stem cells are often resistant to both radiation and chemotherapy and therefore may be responsible for tumor regrowth following treatment. By analogy, cancer stem cells are like the roots of a weed. It is necessary to remove not only the weed but also its roots to prevent the weed from returning, Similarly, the cancer stem cells need to be successfully targeted and eliminated to prevent tumor recurrence. With patient’s consent to use their tumor specimens, our laboratory has now established several patient derived cancer stem cell lines.

Understanding the behavior of the tumor stem cells and how they are able to survive radio- and chemotherapy is necessary to find novel ways to target these cells. Using these cell lines we can evaluate the ability of therapeutic reagents to directly kill these cells or sensitize them to the current treatment regimens. There are over a thousand FDA approved drugs but very few for approved for brain tumor treatment. We can evaluate the potential of reuse these drugs as well as novel drugs and natural compounds to target the cancer stem cells.

Our ultimate goal is to develop a personalized therapeutic approach since tumors although they are histologically diagnosed as being the same tumor type show differences in their molecular and genetic profile. Information on how patient derived cancer stem cells respond to our tested drugs along relevant genetic data will help us reach this goal.

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