Many cancer drugs may not work as thought, CSHL scientists warn

COLD SPRING HARBOR, N.Y., Sept. 11, 2019 /PRNewswire/ -- Scientists at Cold Spring Harbor Laboratory have identified 10 cancer drugs currently in clinical trials that do not work how clinicians thought they would. In identifying what went wrong, experts can now work to improve drug discovery and personalized medicine.

"A lot of drugs that get tested in human cancer patients tragically don't end up helping cancer patients," said Jason Sheltzer, who oversaw the new work.

In a paper recently published in the journal Science Translational Medicine, Sheltzer, along with researchers Ann Lin and Chris Giuliano, detail how the supposed vulnerabilities of cancer targeted by the 10 promising cancer drugs were completely mischaracterized. By revealing the true way these drugs kill cancer cells, Sheltzer and his team hope to "better fulfill the promise of precision medicine."

"If this kind of evidence was routinely collected before drugs enter clinical trials, we might be able to do a better job assigning patients to therapies that are most likely to provide some benefit," he said.

How exactly did they go about revealing the truth behind these drugs?

"The idea for many of these drugs is that they block the function of a certain protein in cancer cells," Sheltzer said. "And what we showed is that most of these drugs don't work by blocking the function of the protein that they were reported to block."

In one example, Sheltzer's team tested a drug designed to block the PBK protein, which is supposedly essential for cancer growth. Proteins such as these are often called cancer "addictions." The researchers revealed that, contrary to prior results, cancer cells are perfectly content to go on living without PBK.

Stranger still, this PBK drug is reportedly helping to kill cancer cells in human clinical trials right now, despite targeting a false addiction. How can this be? The researchers revealed that the drug is also inhibiting the production of another protein known as CDK11 as an off-target or unintentional effect.

"We did an experiment where we gave a very, very high concentration of this drug to cancer cells and then we made the cancer cells evolve a resistance to it," Sheltzer explained. "The cancer cells evolved resistance by mutating CDK11 which, along with some other confirmatory experiments, tells us that CDK11 is what this drug is actually hitting."

Based on that finding, the team plans to explore the promises of CDK11 as an intended drug target, instead of simply a coincidental effect.

About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. For more information, visit http://www.cshl.edu

SOURCE Cold Spring Harbor Laboratory

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