Effective cancer treatment is hampered by tumor hypoxia--a lack of oxygen supplying the cancer cells--rendering cancer cells resistant to therapy. Now a Cancer Research UK funded study has found an antimalaria drug that could reverse tumor hypoxia and complement radiotherapy in killing cancer cells.
The CRUK funded study was headed up by lead author Gillies McKenna from the Medical Research Council Institute for Radiation Oncology in Oxford, where their team published their findings in the journal Nature Communications.
Radiotherapy is a gold standard approach for reducing the size of cancers and it works by creating DNA damage in the target cells causing cell death. A good supply of oxygen reduces the ability of cancer cells to self-repair after DNA damage, and conversely the opposite is true. Therefore an approach to complement radiotherapy is to increase the oxygen supply to the tumor.
To do this the researchers tried out an antimalaria drug, atovaquone. According to the authors the drug appeared to target the mitochondria and slow down the rate at which they use oxygen.
When the researchers did this in mice, they found that by slowing the metabolism of the tumor--the levels of oxygen were increased and when combined with radiotherapy the tumors were more effectively killed.
They validated the drugs antihypoxic behavior in a number of cell lines as well as xenografts from mice. They further tested the drug in mice that were harbouring cancers similar to those found in humans--including lung, bowel, brain and head and neck cancer.
They are now taking these findings to clinical trials to test whether atovaquone is effective in increasing blood supply to tumors in patients with a range of tumors--holding benefit for subsequent radiotherapy treatment.
“This is an exciting result. We have now started a clinical trial in Oxford to see if we can show the same results in cancer patients. We hope that this existing low cost drug will mean that resistant tumours can be re-sensitised to radiotherapy. And we’re using a drug that we already know is safe,” said McKenna in a statement.