New drug compound could reduce spread of brain cancer

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A recent study published in the Scientific Reports has devised an ingenious way to target drugs to brain cancer.

Accounting for 12-15% of all intracranial brain cancers, glioblastoma is one of the most deadly cancers. Glioblastomas are cancer cells that form from abnormal astrocytes. Astrocytes are brain cells that are normally tasked with providing nutrition to the blood vessels supplying the brain.

Despite the combination of surgery, chemotherapy and radiotherapy, the survival rate of glioblastoma is an abysmal 12-15 months. Although there has been growing impetus to discover potential drugs to treat glioblastomas, the ability of these drugs to target the brain presents a major problem. Therefore, this limitation hinders the development of potential treatment options for this devastating brain cancer.

Interstitial fluid is linked to the spread of cancer cells

Interstitial fluid is the fluid occupying the spaces around the cells within tissues. This fluid provides oxygen, nutrition, and biochemical support to the cells and allows for cells to drain the waste products they produce as a result of cellular activities.

In the brain, interstitial fluid accounts for 15-20% of brain volume and is made up of primarily cerebrospinal fluid. Previous studies have shown that in glioblastoma patients, the fluid circulates at a much higher pressure in comparison to normal individuals. This drives tumor cells to spread across the brain tissue.

Current methods to treat brain cancer involve the use of catheters to deliver drugs to GBM patients. However, this process can also increase the convective flow of this interstitial fluid and further worsen the problem.

Drug compound blocks the convective
flow of interstitial fluid and may reduce burden of brain cancer

Investigators from Virginia Tech in the United States investigated if minimizing the distribution of cancer cells due to the convective nature of interstitial fluid could reduce the burden of the disease. They published their results in Scientific Reports.

They first demonstrated that this fluid disseminates cancer cells to other parts of the brain by a convection-powered process that is dependent on a molecule called CXCR4. The researchers then went on to block this protein through an FDA-validated compound that is currently being used in the clinic. This compound is currently called AMD3100.

For this study, the researchers administered the AMD3100 compound at a dose of 5mg/kg and blocked the invasion of glioblastoma cells. They showed that patients that use a convection-enhanced delivery of drugs exhibited a higher level of CXCR4.

More studies needed to determine potential uses

The authors suggested that the use of AMD3100 could be especially beneficial in patients who opt for this method of drug delivery. A large majority of these studies were conducted using a pre-clinical mouse model the disease. Therefore, further in-depth analysis would be required to gather more evidence for potential use in GBM patients.

Written by Vinayak Khattar, Ph.D., M.B.A.

Reference: Cornelison, R. C.,Brennan, C. E., Kingsmore, K. M., & Munson, J. M. (2018). Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model. Scientific Reports, 8(1), 17057.doi:10.1038/s41598-018-35141-9

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