Genetic form of anemia offers new avenue to treating drug-resistant tumors

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The genetic mutation that causes sickle cell anemia also turns red blood cells into potent tumor killers and may offer a new way to treat some cancers that are resistant to existing treatments, according to research published January 9 in the open access journal PLOS ONE by David S. Terman of Jenomic Research Institute and colleagues from Duke University and other institutions.

The mutation that causes sickle cell anemia changes the shape of red blood cells and makes them less efficient at transporting oxygen through the body. When there is little oxygen available in the environment (hypoxia), these sickle cells clump together and block blood vessels, eventually rupturing and damaging the blood vessel and surrounding cells. This is traumatic for those that suffer from the disease, but in this new research, scientists have harnessed this phenomenon to target certain tumors.

Hypoxia is also present in many solid tumors and causes resistance to chemotherapy and radiotherapy. Here, the researchers combined sickled blood cells with a molecule that can release large amounts of oxygen, and injected the cells into mice with severely hypoxic tumors. The sickled cells clumped up within the tumor blood vessels within minutes of injection, blocking tumor blood supply. As they ruptured, the oxygen-releasing molecule they carried also killed a significant proportion of tumor cells and blood vessels. Normal red blood moved freely through the tumors without clumping and did not kill the tumor cells.

Terman explains, "Sickle cells, unlike normal red blood cells, stick like Velcro to tumor blood vessels where they cluster and shut down the blood supply of oxygen deprived tumors. Once clumped within the tumor, the sickle cells rupture releasing toxic residues that promote tumor cell death."

This new approach differs from current treatment of such hypoxic solid tumors by targeting both the cancer cell and surrounding blood vessels suggesting that sickle cells may be "a potent new tool for treatment of hypoxic solid tumors."



INFORMATION:

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

Financial Disclosure: This work was supported by a grant from the National Institutes of Health (NIH) National Cancer Institute (NCI) CA40355-23, -24, -25, -26, 27 to M. W. Dewhirst. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interest Statement: The authors have read the journal's policy and have the following conflicts: DST is sole inventor of US patent 7,803,637 filed August 30, 2000, issued September 28, 2010. All other authors have no competing interests. Dr. David S. Terman is employed by Jenomic. This does not alter his adherence to all the PLoS ONE policies on sharing data and materials. Reovirus Dearing Type 3 was provided by Oncolytics Biotech Inc. (Calgary, Canada). This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

PLEASE LINK TO THE SCIENTIFIC ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (URL goes live after the embargo ends): http://dx.plos.org/10.1371/journal.pone.0052543