OCT 29, 2014 1:30 PM PDT

Metabolic therapy for the adjuvant treatment of malignant brain tumors

Speaker
  • Associate Professor, Neuro-Oncology Research, Barrow Brain Tumor Research Center, Barrow Neurological Institute
    Biography
      Adrienne C. Scheck, PhD, is an Associate Professor at the Barrow Neurological Institute in Phoenix, Arizona. She is also an Adjunct Professor in the School of Life Sciences at Arizona State University and an Associate Investigator in the Cancer Biology Program at the Arizona Cancer Center of the University of Arizona. Dr. Scheck received her undergraduate degree from the University of Rochester in NY and her PhD from Rensselaer Polytechnic Institute in Troy, NY. After a postdoctoral fellowship in viral oncology at the Pennsylvania State College of Medicine in Hershey, Pennsylvania she moved to Memorial Sloan-Kettering Cancer Center to study AIDS-related dementia. She began her studies of brain tumors while at Sloan-Kettering and moved to the Barrow Neurological Institute in 1989. Current work in her laboratory has 2 major goals. The first is to devise novel therapeutic regimens to improve survival and minimize side effects for patients with malignant brain tumors. To this end, her laboratory has been studying the use of the ketogenic diet (KD) for the treatment of malignant brain tumors. Their work has shown that the KD reduces the growth of malignant brain tumors through a variety of mechanisms, and it potentiates the effect of radiation and temozolomide chemotherapy (the standard of care for patients with grade IV brain tumors). These preclinical studies have led to a clinical trial for patients with glioblastoma multiforme (www.clinicaltrials.gov NCT02046187). The second main goal of her research is to identify markers that improve on the current methods of diagnosis and prognosis for this devastating disease. In addition to her love for horses, one of Adriennes pet projects comes from her interest in science education. She directs a program that places high school students in research laboratories and gives Cancer Biology lectures to area high school students, and she was a co-principal investigator on a Science Education grant with the Arizona Science Center.

    Abstract

    Human malignant glioma is a uniformly fatal disease, causing over 14,000 deaths in the US this year. Adults diagnosed with malignant brain tumors have a median survival of approximately 15 months, regardless of currently available treatments which include surgery, radiation and chemotherapy. Improvement in the survival of these patients requires the design of new therapeutic modalities that take advantage of common phenotypes. One such phenotype is the metabolic dysregulation that is a hallmark of cancer cells. This dysregulation causes them to rely preferentially on glucose as an energy source. It has therefore been postulated that one approach to treating brain tumors may be by metabolic alteration such as that which occurs through the use of the ketogenic diet (KD). The KD is high-fat, low-carbohydrate and protein diet that causes a reduction in blood glucose and an increase in blood ketones. It has been utilized for the non-pharmacologic treatment of refractory epilepsy and has a long safety record. We and others have shown that this diet enhances survival in a mouse model of malignant brain tumors when used alone, and we have shown that the KD potentiates the antitumor activity of both temozolomide (TMZ) and radiation. In addition to improvements in survival, the KD appears to reduce peritumoral edema, inflammation, angiogenesis, and cell invasion. Our preclinical data have led to the opening of a clinical trial at the Barrow Neurological Institute using the KD for the upfront treatment of patients with glioblastoma multiforme in addition to radiation and TMZ.

    While the mechanisms through which the ketogenic diet enhances survival have not been fully elucidated, a broad range of gene expression changes have been demonstrated, providing a framework for future studies. An understanding of the mechanisms through which the ketogenic diet exerts its effects will facilitate its use for the treatment of brain tumors in combination with current and future therapeutics.

    Learning objectives:

    • Understand the potential of metabolic alteration in the treatment of malignant brain tumors.
    • Understand some of the mechanisms through which the ketogenic diet alters brain tumor growth.

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