Credit: Rhoda Baer
The drug spironolactone could improve the efficacy of platinum-based chemotherapy by preventing tumor cell repair, according to research published in Chemistry & Biology.
The researchers knew that platinum-based chemotherapy drugs bind to cellular DNA to induce damage.
So they theorized that blocking DNA repair mechanisms would help potentiate chemotherapy by reducing cancer cells’ resistance to treatment.
The team focused their efforts on inhibiting nucleotide excision repair (NER), in which a damaged DNA fragment is replaced with an intact fragment.
Frédéric Coin, PhD, of the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France, and his colleagues screened more than 1200 drugs looking for one that would inhibit NER activity.
And they found that spironolactone—a drug already used to treat fluid retention, high blood pressure, and other conditions—affects NER activity.
Specifically, the team found that, when combined with platinum derivatives, spironolactone significantly increased cytotoxicity in ovarian and colon cancer cells.
As platinum-based chemotherapy is used to treat a range of cancers, similar results might occur in other malignancies as well.
The researchers also noted that, because spironolactone is already in use for other purposes, it doesn’t require a new application for marketing authorization. And its side effects are already known.
The team said this suggests that protocols testing spironolactone in combination with platinum-based chemotherapy could be organized rather quickly.
