Mutation that causes sickle cell anemia may offer new way to treat drug-resistant cancers

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 cancers that are resistant to existing treatments, according to research published January 9, 2013 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 to change the shape of red blood cells also makes them sticky and prone to clump up. When there is little oxygen available in the environment (hypoxia), these sickle cells stick to blood vessel walls, clump together and block their blood supply. The sickle cells eventually rupture damaging the blood vessels and surrounding cells. In this new research, scientists have harnessed this phenomenon to target certain tumors.

Hypoxia is also naturally present in many solid tumors and causes resistance to chemotherapy and radiotherapy. Here, the researchers injected the sickle cells into mice with severely hypoxic tumors. The sickle cells stuck to and clumped up within the tumor blood vessels within minutes of injection, blocking tumor blood supply. As the sickle cells ruptured, the oxygen-releasing molecules they carried combined with a drug that blocked the degradation of such molecules, to kill a significant proportion of tumor cells and blood vessels. In contrast, normal red blood cells moved freely through the tumors without sticking or clumping and did not kill the tumors.

"Sickle cells, unlike normal red blood cells, stick like Velcro to hypoxic tumor blood vessels where they cluster and shut down the tumor blood supply. Once clumped within the tumor, the sickle cells rupture releasing toxic iron residues which promote tumor cell death" said Terman, Head of Molecular Genetics at Jenomic.

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."