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Genetic Form of Anemia Offers New Approach to Treating Drug-Resistant Tumors
By harnessing the qualities that make sickle-cell disease a lethal blood disorder, researchers at Duke University and at a private cancer research company in Carmel, Calif., have developed a way to deploy the misshapen red blood cells to fight cancer tumors.
Reporting in the online journal PLoS One, the researchers describe a process of exploiting sickle-shaped red blood cells to selectively target oxygen-deprived (hypoxic) cancer tumors in mice and block the blood vessels that surround these tumors.
Sickle cells are typically associated with a potentially life-threatening disease in which red blood cells are deformed in the shape of a crescent moon or sickle. Unlike healthy red blood cells that flow smoothly through vessels, the sickle cells get stuck, causing blockages that are painful and damaging to tissue.
According to senior author Mark W. Dewhirst, DVM, PhD, sickle cells stick like Velcro to a hypoxic tumor because the tumor produces an abundance of adhesion molecules as part of its distress from oxygen deprivation. Normal cells don’t produce adhesion molecules, so there is nothing for the sickle cells to snag onto.
“Unlike normal red blood cells, we found that sickle cells show a highly unique natural attraction to oxygen-deprived tumors, where they stick, cluster, and plug tumor blood vessels. Once clustered within the tumor, the sickle cells deposit a toxic iron residue as they die, causing tumor cell death,” said lead author David S. Terman, MD.
To boost that caustic effect, the researchers added zinc compounds (zinc protoporphyrin alone or in combination with doxorubicin) to the sickle cells, which caused even greater oxidative stress in the tumor and surrounding blood vessels. This resulted in a dramatic delay in tumor growth, quadrupling the amount of time the tumors were inactive compared with tumors exposed to regular blood cells.
“In contrast to drug treatments directed only to the hypoxic tumor cell, our approach uses the inherent qualities of sickle cells to induce injury to the tumor and the vascular micro-environment that feed the tumor,” Terman said.
Source: Duke University; January 9, 2013.