Nav: Home

Some cancer drugs in clinical trials don't work by hitting their targets

September 11, 2019

Multiple cancer drug candidates in clinical trials kill tumor cells through off-target effects instead of by interacting with their intended molecular targets, according to a new study. The unexpected findings demonstrate that the targets of these drugs are not essential for the survival of cancer cells - contradicting over 180 previous reports about their importance - and may help explain why seemingly effective cancer drugs often fail to be translated to the clinic. Most cancer drugs that are tested in preclinical and clinical studies never receive FDA approval, largely because the drugs turn out to be too toxic or ineffective in humans. However, it is unclear why so many candidates run into these issues. Ann Lin and colleagues previously discovered that the small molecule OTS167 killed cancer cells by inhibiting proteins other than its designated target. In this study, the authors used CRISPR gene editing techniques to examine the mechanisms of ten other cancer drugs that target one of six proteins, which have been reported as important for the survival of cancer cells in over 180 publications. The drugs studied have been used in at least 29 different clinical trials involving a total of over 1,000 patients, and include prominent candidates such as citarinostat and ricolinostat, which are being tested against multiple myeloma. Contrary to the previous reports based on RNA silencing, the drugs did not actually kill cancer cells by inhibiting their target proteins: they still worked when given to cells deficient in their target. Rather, the drugs induced cell death through off-target mechanisms; for example, the authors found the true target of the drug candidate OTS964 (designed to target the PBK enzyme) was another enzyme named CDK11. Lin et al. argue that it will be necessary to adopt more rigorous genetic approaches in preclinical trials to verify that future drug candidates work as intended.
-end-


American Association for the Advancement of Science

Related Science Articles:

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
AAAS and March for Science partner to uphold science
AAAS, the world's largest general scientific organization, announced Thursday that it will partner with the March for Science, a nonpartisan set of activities that aim to promote science education and the use of scientific evidence to inform policy.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...