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Inside the Lab Genetics and epigenetics, Oncology, Precision medicine, Omics

(Not) All About That Base

The origin of personalized medicine lies in the rapid advancement of genetic analysis in recent years. The cost of looking at a patient’s DNA has dropped precipitously since the transition from Sanger-based to next-generation sequencing to the point where the US$1,000 genome is within our grasp (1). But with this blessing comes a curse – too often, people equate personalized medicine with sequencing, and therefore miss other opportunities for tailoring treatment to individual patients.

Anthony Letai and his research group at the Dana-Farber Cancer Institute (Boston, MA, USA) are taking a different approach. “As an oncologist and a researcher,” Letai says, “it was clear to me that despite a general impression that genetic testing can direct treatment with targeted agents, it does not do this effectively for most patients, and another strategy was needed.” So instead of using genetic analysis, Letai’s team exposes actual tumor cells to a range of cancer drugs and measures their reactions to see whether or not each drug causes apoptotic signaling. “The key is that we make our measurement very early, so that long term ex vivo culture is not required. When we see significant death signaling, it turns out to be a good predictor that the drug will induce a response in vivo. It’s a common sense approach that has been effectively exploited in the microbiology world for many decades in choosing antibiotics to treat bacterial infections.” The technique, called Dynamic BH3 Profiling (DBP), takes less than a day to predict which agents are most likely to work against the tumor in question – providing answers within 16 hours in most cases (2).

Letai is optimistic that the new test could be clinically useful in the future, but only if they can overcome the perception that personalized medicine revolves around sequencing. “In our way of thinking,” he says, “precision medicine is matching the right drugs to the right patient. Genetics is only one tool in doing that, and a tool that will not help direct many drugs in many tumors.” The next step in bringing DBP to the clinic is prospective testing of the assay’s predictive power – it’s a long journey from these preliminary results to full approval, but it’s one Letai hopes will be completed in the next few years.

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  1. KA Wetterstrand, “DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP)” (2014). Available at: http:// Accessed June 4, 2015.
  2. J Montero, et al., “Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy”, Cell, 160, 977–989 (2015). PMID: 25723171.
About the Author
Michael Schubert

While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.

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