Their results are published in Chemistry Biology.
UV rays, physical or chemical agents — the human body is constantly subject to environmental insults that cause more or less damage to our DNA. The body has therefore developed a whole system for proofreading and repair. Among these mechanisms, NER (Nucleotide Excision Repair) has been studied for several years by the researchers in a team led by Frédéric Coin and Jean-Marc Egly at IGBMC. This mechanism can thus detect a lesion, and then replace the damaged DNA fragment with an intact fragment.
Cytotoxic chemotherapy is aimed at blocking the division of malignant cells in order to prevent tumour growth. Included among the drugs used to treat many cancers such as colorectal, face and neck, testicular, bladder, ovarian and lung cancers are medications based on platinum. These drugs bind to cellular DNA, induce damage in the latter, and thus prevent its replication. Blocking DNA repair mechanisms, specifically NER activity, would help to potentiate chemotherapy by reducing the resistance of cells to the treatment.
The researchers at IGBMC therefore sought a drug that would inhibit NER activity. They thus tested over 1,200 therapeutic drugs and demonstrated the action of spironolactone, a drug already used for the treatment of hypertension, on NER activity. Specifically, the researchers showed that its action, when combined with that of platinum derivatives, caused a substantial increase in cytotoxicity for malignant colonic and ovarian cells.
Since spironolactone is already in use for other purposes, it does not require a new application for marketing authorization, and its side-effects are already known. This result thus bodes very well for the rapid development of new chemotherapy protocols that include spironolactone.