09 July 2020
Chemotherapy without lung toxicity now possible
Published online 23 February 2016
Modification of a potent chemotherapy drug eliminates a damaging side effect.
Bleomycin is used to treat lymphomas and cervical and testicular cancers, but lung toxicity, particularly lung fibrosis, is a side effect of the treatment in roughly one-fifth of patients.
The drug consists of two DNA-interacting domains and a sugar domain of unknown function. The team treated mice which had tumours with normal bleomycin and with a version lacking the sugar (called deglyco-bleomycin), which was first synthesized and provided by Abderraouf Kenani of the University of Monastir in Tunisia.
Both treatments were effective at repressing tumours, but only the mice treated with normal bleomycin suffered from side effects of lung toxicity.
“We observed that deglyco-bleomycin has no toxic effect even after intratracheal injection at high doses,” says Philippe Bonniaud of Centre Hospitalier Universitaire in Dijon, who led the study. “That was an exciting moment.”
The team showed that deglyco-bleomycin does not induce the formation of reactive oxygen species which lead to the inflammation of lung tissues.
“This is the first step towards proposing deglyco-bleomycin as an alternative in cancer therapy,” says Bonniaud. “The next step will be to set up a clinical trial with Hodgkin lymphoma patients.”
Burgy, O. et al. Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity. Science Transl. Med. 8, 326ra20 (2016)