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Old Malaria Drug May Have New Role Fighting Cancer

2016-07-29
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An old cancer drug can not only kill cancer cells, but also works to change how certain cancer cells function, weakening those cells so they can be killed by other drugs, a veterinary researcher has discovered.


An off-patent antimalarial, atovaquone, has been utilized to boost cancer-killing capabilities of radiation. Atovaquone came into existence evaluated like a radiotherapy adjunct after it become a standout artist inside a drug screen which was established to identify drugs able to reducing tumor hypoxia.


Tumor hypoxia is known to help cancer cells resist cancer therapy. Cancer cells nestled within low-oxygen tumors resist cancer therapy because they can more easily repair DNA damage, the very thing radiotherapy is used to inflict. Tumors with higher oxygen levels, however, are less adept at DNA repair, and so they are more vulnerable to radiotherapy.


Atovaquone continues to be proven to boost the oxygen amounts of growths, hinder DNA repair in cancer cells, and improve the potency of radiotherapy. This finding, the caused by research carried out in the Cancer Research UK Radiation Research Center, was reported July 25 in the journal Nature Communications, in an article entitled, “The Anti-Malarial Atovaquone Increases Radiosensitivity by Alleviating Tumour Hypoxia.”


“Atovaquone rapidly decreases the OCR [oxygen consumption rate] by more than 80% in a wide range of cancer cell lines at pharmacological concentrations,” wrote the article’s authors. “In addition, atovaquone eradicates hypoxia in FaDu, HCT116, and H1299 spheroids. Similarly, it reduces hypoxia in FaDu and HCT116 xenografts in nude mice, and causes a significant tumour growth delay when combined with radiation.”


According to Cancer Research UK scientists, atovaquone decreases the OCR in cancer cells through its targeting of mitochondria. Specifically, it inhibits mitochondrial complex III.


By slowing down the use of oxygen, atovaquone reverses low oxygen levels in tumors. Then the tumors, now fully oxygenated, may be more easily destroyed by radiotherapy.


Atovaquone was shown to be effective in a wide range of cancers, including lung, bowel, brain, and head-and-neck cancer. This older medicine is no longer patented, and it is readily and cheaply available from generic medicines manufacturers.


“This is an exciting result,” said Professor Gillies McKenna, the lead author of the current study and a researcher at the Cancer Research UK/Medical Research Council Institute for Radiation Oncology in Oxford. “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 tumors can be resensitized to radiotherapy. And we’re using a drug that we already know is safe.”

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