JUL 09, 2015 04:29 PM PDT

Shedding Light on Chemo

Powerful diseases require powerful drugs or powerful doses of drugs, often with severe side effects. An optical control technique for chemotherapy could maximize dosage while minimizing damage.
By using light to inject chemotherapy drugs, researchers can target them to the right cells.
According to a study published in Cell and reported in Science Daily, a new technique using light to activate chemotherapy drugs in specific cells can improve the effectiveness of cancer therapies while preventing severe side effects. The photopharmacology approach could treat a broad range of tumors with great precision by rendering current cancer drugs sensitive to light, which would take less time and effort than typical drug discovery programs (http://www.sciencedaily.com/releases/2015/07/150709132433.htm).

Pharmacotherapy is often severely hindered by issues related to poor drug selectivity, including side effects, environmental toxicity, and the emergence of resistance. Lack of selectivity is caused by the inability to control drug activity in time and space. Photopharmacology aims at solving this issue by incorporating photoswitchable groups into the molecular structure of bioactive compounds. These switching units allow for the use of light as an external control element for pharmacological activity, which can be delivered with very high spatiotemporal precision (http://pubs.acs.org/doi/abs/10.1021/ja413063e).

Co-senior author Oliver Thorn-Seshold of Ludwig-Maximilians-Universität München, explains, "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." He adds that some chemotherapeutic drugs are inhibitors that interfere with the function of microtubules, which are parts of the cell's skeleton that play an important role in cell proliferation, migration and survival. 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. Thus, microtubule inhibitors are usually limited to low doses that fail to give the patient the maximum therapeutic benefit.

To change this paradigm, Thorn-Seshold and his colleagues developed a way to optically control microtubule inhibitor drugs now in clinical trials, with high spatial precision. They have identified a fixed structural element necessary to a drug's biological activity and replaced it with "a flexible hinge that swings open or shut in response to blue light."

Co-senior author Dirk Trauner, also of Ludwig-Maximilians-Universität München, adds, "We can then use light to switch the hinged drug on and off, where and when we want, with single-cell precision. The upshot is that our compounds retain the powerful anticancer effects of existing microtubule inhibitors, but add the bonus of tissue-specific localization."

The team showed the effectiveness of researchers of these modified compounds, called photostatins, at inhibiting the proliferation and survival of cells targeted by light, while not affecting neighboring cells. Photostatins can be switched on and off hundreds of times, enabling their use in long-term applications in both the clinic and the laboratory. Because they target a critical microtubule subunit that is found in the cells of all plants and animals, they can potentially be useful for a broad range of diseases.
About the Author
  • Ilene Schneider is the owner of Schneider the Writer, a firm that provides communications for health care, high technology and service enterprises. Her specialties include public relations, media relations, advertising, journalistic writing, editing, grant writing and corporate creativity consulting services. Prior to starting her own business in 1985, Ilene was editor of the Cleveland edition of TV Guide, associate editor of School Product News (Penton Publishing) and senior public relations representative at Beckman Instruments, Inc. She was profiled in a book, How to Open and Operate a Home-Based Writing Business and listed in Who's Who of American Women, Who's Who in Advertising and Who's Who in Media and Communications. She was the recipient of the Women in Communications, Inc. Clarion Award in advertising. A graduate of the University of Pennsylvania, Ilene and her family have lived in Irvine, California, since 1978.
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