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New Hope for Brain Cancer Therapy

Source: www.lbl.gov
Topic: Brain
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Sort Desciption: Glioblastoma multiforme, the most common of malignant brain tumors in adults, is one of the deadliest of all forms of cancer. Striking some 18,000 new victims in the United States every year ...

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Glioblastoma multiforme, the most common of malignant brain tumors in adults, is one of the deadliest of all forms of cancer. Striking some 18,000 new victims in the United States every year, the disease is always fatal, usually within six months of onset. Surgery and conventional radiation therapies may prolong life for up to a year, but cannot stop the tumors from continuing to spread throughout the brain. Some anticancer drugs show promise against brain tumors, but getting drugs past the blood-brain barrier is a major challenge. Now a collaboration of researchers from Lawrence Berkeley National Laboratory and the Children's Hospital of Oakland Research Institute (CHORI) have demonstrated the potential for nanosized synthetic particles of low density lipoprotein, or LDL, to deliver anticancer drugs to glioblastoma multiforme tumors safely and effectively. "We have identi? ed LDL receptors on glioblastoma multiforme tumor cells that can serve as speci? c molecular targets," says lipoprotein research specialist Trudy Forte. LDL receptors are sparse in normal brain tissue but elevated in tumor cells; the hope is that the synthetic nano-LDLs (nLDLs) can deliver drugs to glioblastoma multiforme tumors while sparing healthy cells. Forte, who has joint appointments in Berkeley Lab's Life Sciences Division and CHORI, led the study with colleagues Mina Nikanjam, Eleanor Blakely, Kathleen Bjornstad, Xiao Shu, and Thomas Budinger. Glioblastoma multiforme is a cancer of the glial cells, which support the neurons and make up about 90 percent of the cells in the brain. As the term multiforme suggests, these cells can take on a wide variety of shapes, making detection dif? cult until tumors become large. Tendrils of malignant cells can extend into healthy brain tissue. If removal or destruction of the main tumor mass leaves tendrils intact, like the mythical Hydra the tendrils will sprout new tumors. One solution would be to follow surgery with anticancer drugs. However, drugs infused in the blood encounter the blood-brain barrier, a tightly knit membrane of cells at the boundary between the central nervous system and the rest of the body that protects the brain from harmful substances in the blood. Because it also blocks anticancer drugs, researchers have long sought a means of circumventing the blood-brain barrier. Previously Forte and coauthor Blakely were part of a team that characterized a tumor-seeking compound known as boronated (proto)-porphyrin, or BOPP, known to concentrate in glioblastoma multiforme tumors. Using the specialized equipment at Berkeley Lab's Life Sciences Microscope Resource, they identi? ed the chemical sites where BOPP binds to glioblastoma multiforme tumors. These binding sites turned out to have the same receptors that take low density lipoproteins into the cell. "Tumor cells generally have high cholesterol requirements as they are rapidly dividing, and LDLs are the major transporters of cholesterol in the plasma," explains Forte. ...

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