Targeting Drug Resistant Tumors

The vibrant colors in the image above show the levels of oxygen saturation in a breast tumor; note the prevalence of shades of dark and light blue, indicating very low oxygen saturation. These tumors are typically very difficult to treat with existing chemotherapy but new research published last week uses sickle cells to target and destroy these types of tumors.

The abnormal type of hemoglobin that causes sickle cell anemia alters the shape of red blood cells from circles to crescents (or sickles) making them less efficient at delivering oxygen to the body’s tissues. When there are low levels of oxygen in the environment, such as at high altitudes, these sickle cells clump together and rupture, damaging the blood vessels and surrounding cells. Honing in on this, researchers from the Jenomic Research Institute and Duke University were able to use this genetic mutation as a way to target tumors and promote a potent tumor-killing response.  Dr. Terman and his team found that they were able to quickly block blood supply to solid tumors with an injection of sickled blood cells along with a molecule that can release large amounts of oxygen. This is demonstrated in the first half of the video below which shows how an infusion of sickled blood cells slows and blocks the blood flow in hypoxic tumors, while the second half shows no noticeable slowing or blockage of blood vessels after infusion of normal cells. The sickled cells then clump together within the tumor blood vessels and when they rupture, the oxygen-releasing molecule kills many of the tumor cells and blood vessels.

This work offers an exciting new avenue for targeting and treating drug-resistant tumors and the video provides a fascinating window into the sickle cells in action.

Citation: Terman DS, Viglianti BL, Zennadi R, Fels D, Boruta RJ, et al. (2013) Sickle Erythrocytes Target Cytotoxics to Hypoxic Tumor Microvessels and Potentiate a Tumoricidal Response. PLoS ONE 8(1): e52543. doi:10.1371/journal.pone.0052543