New Technique For Precise Light-Activated Chemotherapy Drugs

This photo shows incubated human cancer cell lines in cell
culture, treated with our photostatin. Note the contrast in cell
fate for those kept in the dark (left) versus those exposed to
brief pulses of blue light (right).
(Credit: Malgorzata Borowiak, LMU Munich)
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 in the journal 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.
 
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, researchers 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. 
 
The researchers demonstrated that these modified drugs, called photostatins, are effective at inhibiting the proliferation and survival of cells targeted by light, while neighboring cells are unaffected. They can be switched on and off hundreds of times, making them suitable for long-term applications in both the clinic and the lab. Moreover, because they target a critical microtubule subunit that is found in the cells of all plants and animals, they can be used to study or treat a broad range of organisms or processes, even potentially a broad range of diseases in humans.
 
In future clinical settings, the study authors imagine that patients could wear blue-tinted glasses to treat eye cancer or other eye diseases, while individuals with skin cancer could wear a bandage that delivers light to tumors. On the other hand, internal tumors might be treated with an implantable network of tiny LEDs that blink every few minutes to maintain the chemotherapeutic effect only in the enclosed tumor site.
 
In the meantime, the researchers are trying to stretch the limits of their technique with more precise and effective compounds, while refining the technique to treat tumors in mice.
 
 
Based on material originally posted by Cell Press.