A new technique that uses light to activate chemotherapy drugs in specific cells shows promise as a way to improve the effectiveness of cancer therapies while preventing severe side effects, according to a study published July 9 in Cell.
The so-called photopharmacology approach could be used to treat a broad range of tumors with unprecedented precision simply by making existing cancer drugs sensitive to light–an approach that requires less time and effort compared with traditional drug discovery programs.
“We hope that our compounds will one day be used in medicine to deliver a killer blow to many types of localized cancer tumors, without producing side effects, thus improving on standards of care and also providing chemotherapy options for currently untreatable tumors,” says co-senior author Oliver Thorn-Seshold of Ludwig-Maximilians-Universität München.
Some of the most successful and widely used chemotherapeutic drugs are inhibitors that interfere with the function of microtubules–components of the cell’s skeleton that play a key role in cell proliferation, migration, and survival. But because these drugs do not specifically target cancer cells, they also interfere with the function of normal cells and cause severe side effects, such as heart and nerve damage. As a result, microtubule inhibitors are often limited to relatively low doses that do not provide the best therapeutic benefit.
To overcome this challenge, Thorn-Seshold and his collaborators developed a method for optically controlling microtubule inhibitor drugs currently in clinical trials, with high spatial precision. The strategy involves identifying a fixed structural element that is required for a drug’s biological activity, then replacing that element with a flexible hinge that swings open or shut in response to blue light.
“We can then use light to switch the hinged drug on and off, where and when we want, with single-cell precision” says co-senior author Dirk Trauner, also of Ludwig-Maximilians-Universität München. “The upshot is that our compounds retain the powerful anticancer effects of existing microtubule inhibitors, but add the bonus of tissue-specific localization.”