Researchers discover new targets for approved cancer drug

October 10, 2017, H. Lee Moffitt Cancer Center & Research Institute

Developing new drugs to treat cancer can be a painstaking process taking over a decade from start to Food and Drug Administration approval. Scientists are trying to develop innovative strategies to identify and test new drugs quicker and more efficiently. A team of researchers at Moffitt Cancer Center used cellular drug screening, functional proteomics and computer-based modeling to determine whether drugs with well-known targets may be repurposed for use against other biological targets. They found that an FDA approved drug for non-small cell lung cancer called ceritinib has anti-cancer activity against previously unknown targets. Their results were published today in the journal, Nature Chemical Biology.

For the past 20 years, there has been an emphasis on targeted - targeting a specific driver of cancer development to minimize side effects typically seen with chemotherapy. This personalized approach has been successful in certain types of cancer that are primarily driven by a single DNA alteration, such as found in . However, the majority of cancers are not caused by a single mutation; rather, cancer is more commonly caused by a large network of mutations and alterations. Some researchers, including those from Moffitt, are beginning to rethink the targeted approach to cancer therapy. They believe that developing drugs that act on multiple targets, called a polypharmacology approach, may more effectively treat those cancers that have a network of alterations.

In order to identify drugs that act on multiple targets, Moffitt researchers screened 240 drugs that are either FDA approved or in clinical development. They noticed that the ceritinib acts differently than other drugs in its class. Ceritinib targets a protein called ALK, and is approved to treat patients with ALK-rearranged metastatic non-small cell lung cancer. Their research found that ceritinib also inhibits the growth of that do not have genetic alterations in the ALK gene.

After an extensive set of experiments to learn how ceritinib worked in cells without ALK rearrangements, they discovered the drug inhibits several other previously unknown targets, and that these signals converge onto a protein known to be responsible for causing drug resistance to paclitaxel. Importantly, the researchers showed that ceritinib combined with paclitaxel was more effective than either agent alone at reducing cell viability.

These findings suggest that ceritinib together with paclitaxel may be effective against other cancers that do not have ALK rearrangements, and that this drug combination may be used to target a network of changes in .

"The results also demonstrate the benefits of using a combined screening, proteomics and computer-based modeling approach to identify drugs that act on multiple targets and to determine how they function," said study lead author Uwe Rix, Ph.D., assistant member of the Drug Discovery Program at Moffitt. "In the future, this strategy may facilitate further drug repurposing efforts and lead to an increase in new therapy options for patients with difficult-to-treat diseases."

Explore further: New use for alcohol aversion drug in treatment of chemo resistant lung cancer found

More information: Brent M Kuenzi et al. Polypharmacology-based ceritinib repurposing using integrated functional proteomics, Nature Chemical Biology (2017). DOI: 10.1038/nchembio.2489

Related Stories

Ceritinib in advanced lung cancer: No hint of added benefit

October 6, 2015

The drug ceritinib (trade name: Zykadia) has been approved since May 2015 for the treatment of adults with non-small cell lung cancer (NSCLC). It is an option when certain changes in the cancer cells (anaplastic lymphoma ...

Recommended for you

A protein that self-replicates

February 22, 2018

ETH scientists have been able to prove that a protein structure widespread in nature – the amyloid – is theoretically capable of multiplying itself. This makes it a potential predecessor to molecules that are regarded ...

Squid skin could be the solution to camouflage material

February 22, 2018

Cephalopods—which include octopuses, squid, and cuttlefish—are masters of disguise. They can camouflage to precisely match their surroundings in a matter of seconds, and no scientist has quite been able to replicate the ...

The cryo-electron microscopy structure of huntingtin

February 22, 2018

Mutations on a single gene, the huntingtin gene, are the cause of Huntington's disease. They lead to an incorrect form of the correspondent protein. With the help of cryo-electron microscopy researchers from the Max Planck ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.