Brain tumors are the second only to leukemias as the most common malignancies in children, and they continue to present a difficult management problem. While cure rates are improving, survival is still poor, and survivors suffer from serious long-term side effects of the therapy.
To improve the outcome for children diagnosed with brain tumors, including medulloblastoma, the Cancer Epigenetics Lab, headed by Sigrid A. Langhans, PhD, is taking three complementary approaches to its pediatric cancer research:
Curcumin, chemically known as diferuloylmethane, is a spice derived from the rhizomes of the plant Curcuma longa. Curcumin has anti-cancer properties with no discernible toxicity. Using cultured medulloblastoma cells and a transgenic medulloblastoma mouse model, researchers have shown that curcumin can reduce tumor growth in vitro and in vivo.
Dr. Langhans has now identified a novel molecular target of curcumin, the anaphase-promoting complex (APC) component Cdc27/APC3, that could be used as a biomarker to predict which patients respond to curcumin-based therapy. In addition, a full patent application is being submitted claiming Cdc27 not only as a biomarker, but also as a target for drug development of novel anti-cancer drugs.
Nanotechnology-based Approaches for Improved Drug Delivery to the Brain
To circumvent the blood-brain barrier, a natural impediment for efficient drug delivery to the brain, researchers at the Cancer Epigenetics lab are developing, in collaboration with the Department of Materials Science and Engineering at the University of Delaware, a nano-hydrogel approach for direct drug delivery to brain tumors. Initial studies confirmed that the hydrogels are suitable drug carriers with a sustained drug release profile. The project was supported by the Center of Biomedical Research Excellence (COBRE) at the University of Delaware.
Novel Drug Targets
The lab is studying the molecular biology of brain tumor development to identify novel drug targets. Na,K-ATPase, well known as an ion pump required for the normal functioning of neurons, has recently been shown to have additional functions in oncogenic signaling and cell adhesion. The research group of Dr. Langhans now found that Na,K-ATPase is a molecular target of Sonic hedgehog signaling, a developmental pathway commonly affected in medulloblastoma. Funding has been secured to characterize the signaling pathways leading to loss of Na,K-ATPase expression in medulloblastoma and to define the pathological consequences in brain tumor progression.
Based on this work a patent application was submitted during 2012: “Method for identifying therapeutic agents for treatment of cancer.”