More Data, More Problems – New Group Sheds Genomics in Favor of Practical Approaches

Written by Bioscribe and Tony Letai on August 02, 2018

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When it comes to modern medicine, Tony Letai prefers to go old school.

Keep it simple, he says. Simple assays. Simple analysis.

Keep it real, he says. Real patient samples. Real-time results.

And if, like him, you’re “just a dumb doc who wants to put drugs on cancer cells,” then perhaps you should join him.

Letai, founder of The Society for Functional Precision Medicine, advocates ditching cumbersome, costly and time consuming big data genomic approaches to precision medicine in favor of rapid testing methods that expose living patient tumor cells directly to the drugs that could be used to treat them.

As he argues in a Nature Perspectives piece previously featured on this blog and in a recent Mendelspod interview, the promise of the precision medicine that has been pitched to the public for the past decade is not being delivered to most patients. Only a small subset of patients are benefitting from deep dives into their genomes.

Why base treatment decisions on dead cells that have been out of the body for 7, 14, or even 21 days - time in which the patient’s cancer has likely evolved? Why collect terabytes of data that have to then be analyzed and interpreted, with many non-relevant or confusing results? Why rely on a technology that cannot differentiate from blood cells and fingernails?

Instead, you could collect patient cells and expose them to potential treatments within 24 hours, while they are still alive, and get real-time results that are immediately actionable. It may not tell you huge amounts of information about the tumor’s biology, but that’s not the goal of precision medicine, he says.

“The top priority of precision medicine is to identify drugs that work for a particular patient’s tumor, and I think we need to rediscover functional tools that have been left by the wayside a decade or two ago,” Letai told Mendelspod host Theral Timpson.

“This is not a new idea,” he added. “This is what we do in microbiology. This is the gold standard for figuring out what antibiotic drugs we give patients with a particular bacterial infection, to expose the actual bacteria to the actual drugs and see the one that works the best.”

Although once questioned as a “dumb doc” by a Nobel laureate, Letai is no dummy. The associate professor at Harvard Medical School and the Dana Farber Cancer Institute holds both an M.D. and Ph.D., and is also an associate member of the Broad Institute. Neither are his fellow SFPM founders: Chris Kemp, Ph.D., of the Fred Hutchinson Cancer Research Center; Jeff Tyner, Ph.D., of Oregon Health Sciences University; and Keith Ligon, M.D., Ph.D., also of Harvard and Dana Farber.

All of them believe that returning to the fundamentals may provide simple solutions that are more effective to meeting the mission of precision medicine than current approaches, which are often too smart for their own good.

They’re not abandoning the advances of technology to do so. Many embrace it, using a variety of modern methods in a variety of ways, from organoids and 2-D cultures to implantable devices and advanced rapid ex-vivo measurements. For example, Echo Liquid Handlers are central to the work of SFPM member and Labcyte collaborator Krister Wennerberg, whose work while at the Institute for Molecular Medicine Finland (FIMM), is highlighted in this video.

And Letai has already proved the simple approach can deliver sophisticated, practice-changing results. He was able to use these approaches to identify cells that were BCL2 dependent and particularly sensitive to a certain drug that has now transformed the treatment of chronic lymphocytic leukemia (CLL), with 40-50 clinical trials in the US alone.

“Our overriding mission is to accelerate the day when functional assays are a routine tool in the care of the cancer patients,” Letai states on the Society site. “We propose to bring cutting edge tools of tissue culture and analysis to bear on this strategy to create practical solutions.”

He’s inviting like-minded scientists, clinicians, regulators, clinical trial designers and pathologists to join the SFPM, which is an all-encompassing international science-sharing, advice-giving advocacy and networking group founded in 2017 and officially launched at AACR 2018.

For more information about SFPM, visit www.sfpm.io.

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