MARC U*STAR

Justin Saul, Ph.D.

Justin Saul PhD photo

Gliomas, particularly glioblastoma multiform (GBM), are among the most virulent of cancers. Twenty years of research has yielded little improvement in clinical outcomes with an average survival of one year and five year survival rates of less than 10%[1]. Standard therapy for GBM patients is surgical resection followed by a course of radiation therapy[2]. The use of chemotherapy is controversial, with few treatments showing clear therapeutic benefit. Several limitations to successful use of chemotherapy are multi-drug resistance and inability to localize drugs to tumor cells due the presence of the blood brain barrier.

As an approach to overcome these two barriers, we are utilizing nanoscale drug delivery systems targeted toward cell surface receptors over-expressed by tumor cells. Simultaneous delivery of multiple chemotherapeutic agents that target alternative pathways is potentially advantageous in achieving greater toxicity in tumor cells. Nanoscale carriers such as liposomes provide a method to achieve this simultaneous delivery by incorporation of drugs into a single carrier. Further, targeting ligands directed at uniquely expressed or highly over-expressed surface receptors on glioma cells can achieve intracellular delivery for increased selectivity of the drug carriers and their payloads.


References

  1. Davis FG, Freels S, Grutsch J, Barlas S, Brem S. Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973- 1991. J Neurosurg 1998;88(1):1-10.
  2. Bleehen NM, Stenning SP. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. Br J Cancer 1991 Oct;64(4):769-774.

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