Antibiotics may help to treat melanoma

Some antibiotics appear to be effective against a form of skin cancer known as melanoma. Researchers at KU Leuven, Belgium, examined the effect of these antibiotics on patient-derived tumours in mice. Their findings were published in the Journal of Experimental Medicine.

Researchers from KU Leuven may have found a new weapon in the fight against melanoma: antibiotics that target the 'power plants' of cancer cells. These antibiotics exploit a vulnerability that arises in tumour cells when they try to survive cancer therapy.

"As the cancer evolves, some melanoma cells may escape the treatment and stop proliferating to 'hide' from the immune system. These are the cells that have the potential to form a new tumour mass at a later stage" explains cancer researcher and RNA biologist Eleonora Leucci (KU Leuven). "In order to survive the cancer treatment however, those inactive cells need to keep their 'power plants' - the mitochondria - switched on at all times". As mitochondria derive from bacteria that, over time, started living inside cells, they are very vulnerable to a specific class of antibiotics. This is what gave us the idea to use these antibiotics as anti-melanoma agents."

The researchers implanted patient-derived tumours into mice, which were then treated with antibiotics - either as the only treatment or in combination with existing anti-melanoma therapies. Leucci: "The antibiotics quickly killed many cancer cells and could thus be used to buy the precious time needed for immunotherapy to kick in. In tumours that were no longer responding to targeted therapies, the antibiotics extended the lifespan of - and in some cases even cured - the mice."

The researchers worked with antibiotics that are now, because of rising antibiotic resistance, only rarely used in bacterial infection. However, this resistance has no effect on the efficacy of the treatment in this study, explains Leucci. "The cancer cells show high sensitivity to these antibiotics, so we can now look to repurpose them to treat cancer instead of bacterial infections."

However, patients with melanoma shouldn't start experimenting, warns Leucci. "Our findings are based on research in mice, so we don't know how effective this treatment is in human beings. Our study mentions only one human case where a melanoma patient received antibiotics to treat a bacterial infection, and this re-sensitised a resistant melanoma lesion to standard therapy. This result is cause for optimism, but we need more research and clinical studies to examine the use of antibiotics to treat cancer patients. Together with oncologist Oliver Bechter (KU Leuven/UZ Leuven), who is a co-author of this study, we are currently exploring our options."

Vendramin R, Katopodi V, Cinque S, Konnova A, Knezevic Z, Adnane S, Verheyden Y, Karras P, Demesmaeker E, Bosisio FM, Kucera L, Rozman J, Gladwyn-Ng I, Rizzotto L, Dassi E, Millevoi S, Bechter O, Marine JC, Leucci E.
Activation of the integrated stress response confers vulnerability to mitoribosome-targeting antibiotics in melanoma.
J Exp Med. 2021 Sep 6;218(9):e20210571. doi: 10.1084/jem.20210571

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