Precision Oncology: Gene Changes Predict Immunotherapy Response

Cancer Immunotherapy

Caption: Adapted from scanning electron micrograph of cytotoxic T cells (red) attacking a cancer cell (white).
Credits: Rita Elena Serda, Baylor College of Medicine; Jill George, NIH

There’s been tremendous excitement in the cancer community recently about the life-saving potential of immunotherapy. In this treatment strategy, a patient’s own immune system is enlisted to control and, in some cases, even cure the cancer. But despite many dramatic stories of response, immunotherapy doesn’t work for everyone. A major challenge has been figuring out how to identify with greater precision which patients are most likely to benefit from this new approach, and how to use that information to develop strategies to expand immunotherapy’s potential.

A couple of years ago, I wrote about early progress on this front, highlighting a small study in which NIH-funded researchers were able to predict which people with colorectal and other types of cancer would benefit from an immunotherapy drug called pembrolizumab (Keytruda®). The key seemed to be that tumors with defects affecting the “mismatch repair” pathway were more likely to benefit. Mismatch repair is involved in fixing small glitches that occur when DNA is copied during cell division. If a tumor is deficient in mismatch repair, it contains many more DNA mutations than other tumors—and, as it turns out, immunotherapy appears to be most effective against tumors with many mutations.

Now, I’m pleased to report more promising news from that clinical trial of pembrolizumab, which was expanded to include 86 adults with 12 different types of mismatch repair-deficient cancers that had been previously treated with at least one type of standard therapy [1]. After a year of biweekly infusions, more than half of the patients had their tumors shrink by at least 30 percent—and, even better, 18 had their tumors completely disappear!

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Built for the Future. Study Shows Wearable Devices Can Help Detect Illness Early

Michael Snyder wearing monitors

Caption: Stanford University’s Michael Snyder displays some of his wearable devices.
Credit: Steve Fisch/Stanford School of Medicine

Millions of Americans now head out the door each day wearing devices that count their steps, check their heart rates, and help them stay fit in general. But with further research, these “wearables” could also play an important role in the early detection of serious medical conditions. In partnership with health-care professionals, people may well use the next generation of wearables to monitor vital signs, blood oxygen levels, and a wide variety of other measures of personal health, allowing them to see in real time when something isn’t normal and, if unusual enough, to have it checked out right away.

In the latest issue of the journal PLoS Biology [1], an NIH-supported study offers an exciting glimpse of this future. Wearing a commercially available smartwatch over many months, more than 40 adults produced a continuous daily stream of accurate personal health data that researchers could access and monitor. When combined with standard laboratory blood tests, these data—totaling more than 250,000 bodily measurements a day per person—can detect early infections through changes in heart rate.

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Happy New Year: Looking Back at 2016 Research Highlights

Science Breakthroughs of the Year 2016Happy New Year! While everyone was busy getting ready for the holidays, the journal Science announced its annual compendium of scientific Breakthroughs of the Year. If you missed it, the winner for 2016 was the detection of gravitational waves—tiny ripples in the fabric of spacetime created by the collision of two black holes 1.3 billion years ago! It’s an incredible discovery, and one that Albert Einstein predicted a century ago.

Among the nine other advances that made the first cut for Breakthrough of the Year, several involved the biomedical sciences. As I’ve done in previous years (here and here), I’ll kick off this New Year by taking a quick look of some of the breakthroughs that directly involved NIH support:

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Precision Medicine: Using Genomic Data to Predict Drug Side Effects and Benefits

Gene Variant and Corornary Heart DiseasePeople with type 2 diabetes are at increased risk for heart attacks, stroke, and other forms of cardiovascular disease, and at an earlier age than other people. Several years ago, the Food and Drug Administration (FDA) recommended that drug developers take special care to show that potential drugs to treat diabetes don’t adversely affect the cardiovascular system [1]. The challenge in implementing that laudable exhortation is that a drug’s long-term health risks may not become clear until thousands or even tens of thousands of people have received it over the course of many years, sometimes even decades.

Now, a large international study, partly funded by NIH, offers some good news: proof-of-principle that “Big Data” tools can help to identify a drug’s potential side effects much earlier in the drug development process [2]. The study, which analyzed vast troves of genomic and clinical data collected over many years from more than 50,000 people with and without diabetes, indicates that anti-diabetes therapies that lower glucose by targeting the product of a specific gene, called GLP1R, are unlikely to boost the risk of cardiovascular disease. In fact, the evidence suggests that such drugs might even offer some protection against heart disease.

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Creative Minds: Stretching the Limits of Wearable Devices

Darren Lipomi

Darren Lipomi/ Credit: UC, San Diego

Whether it’s a pedometer dangling from a belt loop or a skin patch to monitor heart rate and hydration levels, wearable and mobile devices have become essential gear for many of today’s fitness minded. But Darren Lipomi, a nanoengineer at the University of California, San Diego, envisions even more impressive things to come for optimizing workouts and bringing greater precision to health care. Lipomi is helping to build a future of “stretchable electronics,” semiconducting devices that will more seamlessly integrate with the contours of our bodies, outside and even inside, to monitor vital signs, muscle activity, metabolic changes, and organ function—to name just a few possibilities.

Lipomi and his colleagues specifically want to create a new class of semiconducting polymer that has the mechanical properties of human skin. This transparent “electronic skin” will have a soft elasticity to conform to shape, sense contact, absorb blunt force, and even self heal when dinged. It will do all of this—and possibly more—while continuously and wirelessly performing its programmed health-monitoring function. To help Lipomi build this future of real-time health monitoring, he has been awarded a 2015 NIH Director’s New Innovator Award. This NIH award supports exceptionally creative new investigators who propose highly innovative projects with the potential for unusually high impact.

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