Optogenetics identifies receptor linked to cancer, expanding into drug discovery

A team of scientists at the Institute of Science and Technology Austria (IST Austria; Klosterneuburg, Austria) employed optogenetics (the use of light to control genetically modified cells) to identify a new compound that inhibits the orphan receptor ROS1, which has been linked to several forms of cancer. The researchers' work is promising for expanding optogenetics into the field of drug discovery.

Related: Light now able to activate cell surface receptors, with promising implications

The researchers demonstrated the power of optogenetics by carrying out a screen against 'orphan' receptors, the receptors for which the natural ligand is currently unknown. Therefore, orphan receptors can only be activated in cells using a synthetic approach, such as the artificial light switch introduced in their study. Using the optical screening method, the researchers identified a new active compound that binds to and inhibits ROS1, an orphan receptor that plays a role in a variety of cancers. The inhibitory compound AV-951, also known as Tivozanib, has already been studied in clinical trials and has the potential to treat many forms of cancer.

(L-R) Postdoc Álvaro Inglés-Prieto, PhD student Eva Reichhart, and Assistant Professor Harald Janovjak, whose work using optogenetics identified a receptor linked to many forms of cancer
(L-R) Postdoc Álvaro Inglés-Prieto, PhD student Eva Reichhart, and Assistant Professor Harald Janovjak, whose work using optogenetics identified a receptor linked to many forms of cancer.

In the study, the researchers used light as both the activator and the readout of cellular signaling without needing assay chemicals, which limits the number of steps required in carrying out the screen. By using LEDs, activation is both cheap and highly specific.

Full details of the work appear in the journal Nature Chemical Biology; for more information, please visit http://dx.doi.org/10.1038/nchembio.1933.

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