Nature Medicine Perspective Piece on Functional Precision Cancer Medicine


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In a recent Perspective piece in Nature Medicine, Dana Farber cancer researcher Tony Letai, M.D., Ph.D., makes a compelling case for focusing more attention and resources on the functional application of precision medicine, rather than pure genomics.

Referencing “sobering recent studies” that suggest most patients who receive genomic testing do not ultimately benefit from a precision medicine treatment strategy, Letai suggests returning to a basic principle employed in the physical sciences: perturbing a system and carefully measuring what happens next.

As an analogy, he uses a dog and stick. To predict what would happen if you poke a dog with a stick, you could simply poke a dog with a convenient stick and see what happens (the functional approach). Or you could kill the dog, sample its tissues for genomic, proteomic and metabolomics measurements at the initial condition, and somehow use those terabytes of analytically accurate information to make a prediction (the current precision medicine approach). Although there are far fewer bits of data involved with the functional approach, Letai argues that the data acquired are much more relevant and actionable.

In oncology, the ‘stick’ used to poke cancer cells would be a drug, or combination of drugs.

Letai goes on to outline several ways in which this functional approach is being applied, including the Drug Sensitivity and Resistance Testing (DSRT) platform pioneered by Krister Wennerberg and colleagues at the Institute for Molecular Medicine Finland (FIMM), a Labcyte collaborator. Letai’s own Dynamic BH3 profiling approach involves dissociating tumor samples into single-cell suspensions, distributing them into 384-well plates, applying drugs to the wells, and measuring BH3 profiles to determine changes in apoptotic signaling.

He says information about what happens when a patient’s actual cancer cell encounters an actual drug is crucial to collect – otherwise, “we will be fighting cancer with one hand tied behind our backs.”

One of the challenges the field of functional genomics faces is a perception that such approaches are somewhat crude and unsophisticated, Letai notes.

But today’s technological ‘sticks’ are far from crude, as demonstrated by Labcyte Echo® Acoustic Liquid Handlers. These powerful tools are enabling innovative companies such as Notable Labs and SEngine Precision Medicine, as well as several centers in Europe, to better tailor cancer therapies to individual patients, increase the understanding of mechanisms of action of drugs and identify opportunities to re-purpose drugs. The work at FIMM has directly led to the surprising discovery that an approved renal cancer drug looks to be effective for treating one form of leukemia, leading to that drug now being under clinical study.

We agree that functional drug screening added to translational genomics is the future of precision medicine, and we are proud to be able to provide a critical technology that will move the industry in that direction.