Liquid Biopsies Give Clues on When and Why Cancer Treatments Lose their Efficacy

With the advent of targeted cancer therapies and immunotherapy, and with new CAR-T therapies on the way, more cancer patients are living with their disease. However, many cancer patients find that their therapies have limitations and are faced with the potential of disease progression. Often, those who initially respond to a course of treatment eventually develop a resistance to these medications, forcing oncologists to switch therapeutic course.

Currently, one of the ways to know when a treatment stops working is by taking a biopsy of the tumor. These surgical procedures are invasive and costly, and because they can only be done sporadically, valuable treatment time can be lost. Additionally, some cancer patients may be too physically fragile for surgery.

Researchers have been looking for a safe, fast, less expensive and more accurate way to identify early signs of treatment resistance, while also searching for new insights into the genetic changes that occur within tumor cells to drive this resistance. This way, new therapy plans can be considered sooner, giving the patient a better chance for their best possible outcome.

A new diagnostic blood test known as a liquid biopsy has shown early promise in addressing these needs. Now researchers, including a team from the Mass General Cancer Center, are providing confirmatory data that may help to move liquid biopsies into clinical practice. These data were presented at the ESMO 19th World Congress on Gastrointestinal Cancer.

How do liquid biopsies work?

A liquid biopsy is a diagnostic test that detects circulating tumor DNA (ctDNA), which is genetic material released by dying tumor cells that flows through the bloodstream. These tests are less invasive than a tissue biopsy and therefore can be given with greater frequency.

Regularly monitoring ctDNA levels in a patient’s bloodstream can provide early notice when a treatment is no longer working. It could also offer a more complete picture of the genetic changes in tumor cells that are driving the resistance to treatment, which could guide new treatment courses.

Liquid biopsies and gastrointestinal cancer study

Mass General Cancer Center investigators followed nearly 40 patients with various forms of gastrointestinal cancers who had experienced initial success with targeted therapies, but then began to show signs of treatment resistance. Liquid biopsies were taken when the patients’ disease started to progress to analyze the levels and genetic profile of ctDNA in their bloodstream. Researchers identified one or more mutations or mechanisms that contributed to treatment resistance in 31 of the 40 patients. Fourteen of these patients had multiple mutations that contributed to resistance.

In patients who had both solid tissue biopsies and the liquid biopsies, the researchers found that in two-thirds of the cases, the liquid biopsies revealed the presence of more genetic mutations than tissue biopsies alone.

“Identifying what specific mutations are responsible for treatment resistance is very important in helping clinicians choosing what treatment path a patient should try next, whether it be another drug or perhaps radiation,” said study investigator Aparna Parikh, MD, from the Mass General Cancer Center.

“We have shown this approach is feasible across many different GI cancers,” she noted. “The next step is to study how best to use this new technology in daily practice. It’s important for clinicians to understand its utility as well as its limitations.”

Meet our Fall Communications Intern!

Please join us in welcoming Nishtha Yadav, a graduate student at Emerson College and our communications intern this semester. Be sure to check back here for updates on what she’s working on!



Nishtha Yadav

Where do you attend school and what’s your major, and year?

I’m a second year Communication Management graduate student at Emerson College.

Where are you from?

I currently live in Brookline, but I’m originally from New Delhi, India.

Why are you interning at the Mass General Research Institute?

I wanted to get a glimpse of how a leading research institute pushes out information to their stakeholders about clinical trials and research conducted at the hospital and its affiliates. As someone who enjoys writing long-form, research-oriented articles and has an avid interest in learning more about the healthcare industry, this internship was a perfect fit for me.

What do you hope to gain or learn while interning here?

Previously, I worked as a reporter with a leading English daily in India and did not get an opportunity to write research based articles due to the 24/7 news cycle. So, I hope I’m able to strengthen my research and writing skills.

Also, by the end of my internship, I hope I’ve a better sense of scientific/health industry terminology, which would help me in understanding complex research being conducted by scientists and clinicians.

Why are you interested in health communications?

This summer, I interned at Dana-Farber Cancer Institute and had an opportunity to be a part of their radio-telethon, where all the patients, researchers and doctors were present to raise funds for cancer research. I saw patients, right from babies to octogenarians, and their families who couldn’t stop thanking their doctors for saving their lives. That’s when I realized that communicating with the public about medical breakthroughs and treatments is of utmost importance – it can save lives!

What are your future/career goals?

I would like to work either in the nonprofit sector or work as a crisis management professional. Years from now, I also see myself running for public office in India.

Secretly, I’m hoping that I’ll be discovered by Ryan Murphy and become the next Sarah Paulson! (Murphy is the creator of the American Horror Story, Glee, People vs. O.J. Simpson, etc., and Paulson is an award-winning actress, famous for her work in the American Horror Story and People vs. O.J. Simpson)

What do you like to do when you’re not being an intern?

Apart from planning my Oscar acceptance speech and binge-watching Netflix, I try to listen to as many podcasts as I can and read as much as I can, while trying different varieties of herbal tea.

Favorite dinosaur?

Dino from The Flintstones. Just kidding! Argentinosaurus is my favorite dinosaur. I always get the sense that they were free-willed and walked around their natural habitat like a king/queen.

Favorite food?

My mother has an elaborate recipe for cottage cheese (called Paneer in South Asia) – it’ll always be my favorite food.

HUBweek Art of Talking Science Competition Recap


Last Wednesday the Mass General Research Institute hosted The Art of Talking Science: Rise of the Machines at the Russell Museum at Massachusetts General Hospital.

As part HUBweek’s weeklong festival, this science communication competition challenged researchers focused on artificial intelligence, machine learning and digital health to present their science in four minutes or less. Each contestant received feedback from a panel of celebrity judges and, at the end, one presenter was crowned the winner.

Here’s a look back at some of the highlights from the afternoon:

Opening Remarks

Sue Slaugenhaupt, PhD, Scientific Director of the Research Institute, gave an introduction on the importance of communicating science.

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Sue Slaugenhaupt, PhD


Meet the Judges

Dr. Slaugenhaupt also introduced our panel of judges who each spoke for a few minutes about what science communicating means to them.

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Our amazing judges, were (from left): Ike Swetlitz, Reporter for STAT News, Rich Hayes, Creative Director/Deputy Director of Communications for the Union of Concerned Scientists, Carey Goldberg, Editor for the WBUR CommonHealth Blog, and Christine Reich, PhD, Vice President of Exhibit Development and Conservation at the Museum of Science, Boston.

Keynote Presentation

Then judge Christine Reich gave a keynote presentation discussing how the Museum of Science empowers their guests through science communication.

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Christine Reich, PhD

After Dr. Reich’s fascinating presentation, the competition began!

The Competition

Justin Baker, MD, PhD, went first with his presentation, Exploring the Human-Human Interface. Dr. Baker is Scientific Director at the Institute for Technology in Psychiatry and an Assistant Psychiatrist at McLean Hospital.

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Justin Baker, MD, PhD

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Kamal Jethwani, MD, MPH, Senior Director of Connected Health Innovation, Partners Connected Health, then gave a slideless presentation entitled, Want to Lose 5 Lbs Fast? Artificial Intelligence Holds the Key.

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Kamal Jethwani, MD, MPH


Our third presenter was Jacob Dal-Bianco, MD, who spoke about preventing rheumatic heart disease. Dr. Dal-Bianco is a cardiologist at Massachusetts General Hospital.

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Jacob Dal-Bianco, MD

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David Gow, PhD, of the Cognitive/Behavioral Neurology Group at Massachusetts General Hospital, then gave his presentation, Using Machine Learning to Help the Brain Understand Itself.

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David Gow, PhD

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Up next was Lisa Gualtieri, PhD, ScM, who discussed a lending library for fitness trackers. Dr. Gualtieri is the founder of Recycle Health, an Assistant Professor in the Department of Public Health and Community Medicine at Tufts University School of Medicine, and the Director of the Digital Health Communication Certificate Program.

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Lisa Gualtieri, PhD, ScM

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Closing out the program was Roland Carlstead, PhD, of the Developmental Biology Research Program at McLean Hospital. Dr. Carlstead discussed whether treatment works and if the placebo effect is real.

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Roland Carlstedt, PhD

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After much deliberation, the judges named Justin Baker as the winner.

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Thank you to all our contestants and the judges for their insightful feedback and support of science communication!



Four Massachusetts General Hospital Researchers Receive Prestigious NIH Director’s Awards

Please join us in congratulating the four Mass General investigators who recently received director’s awards from the National Institutes of Health (NIH)! These awards are given to exceptionally creative scientists who propose innovative approaches with high-impact potential to major challenges in biomedical research.

Continue reading to learn more about each researcher and their proposed work as well as their reaction to receiving this award.

New Innovator Award

The New Innovator Award supports exceptionally creative early career investigators who propose innovative, high-impact projects.

Evan Macosko, M.D., Ph.D.
Broad Institute of MIT and Harvard, Massachusetts General Hospital

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“I am delighted and honored that the NIH is willing to support this high-risk technology project.  The lab can’t wait to get started on some potentially very impactful scientific work.”

Project Title: Slide-Seq: High-Resolution In Situ Expression Profiling for Neuropathology
Grant ID: DP2-AG-058488

Evan Macosko is a principal investigator in the Stanley Center for Psychiatric Research at the Broad institute, and an Assistant Professor of Psychiatry at Harvard Medical School. His research focuses on developing and leveraging new technologies in genomics to characterize pathophysiological mechanisms in neuropsychiatric diseases. As a postdoc in Steven McCarroll’s lab at Harvard Medical School, he developed a new method, Drop-seq, for performing highly parallel gene expression analysis of single cells from complex neural tissues. He completed a psychiatry residency at MGH and McLean Hospital, and is currently an attending psychiatrist at MGH. He holds a Ph.D. in Neuroscience and Genetics from Rockefeller University, and an M.D. from Weill Cornell Medical College.

Radhika Subramanian, Ph.D.
Massachusetts General Hospital and Harvard Medical School

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“I am extremely grateful and honored to receive the NIH Director’s New Innovator Award. The support provided by this award will allow my lab to pursue a new research direction where we will develop a versatile cell-free imaging platform that will enable us to decipher how spatial cues are encoded and decoded within cells. We expect that the toolkit established here will be applicable for elucidating the fundamental mechanisms that govern the spatial organization of cellular reactions that underlie diverse cell-­biological  processes of biomedical significance such as cell division, migration, and development.”

Project Title: A Versatile Platform for Reconstructing the Spatial Organization of Intracellular Signaling During Cell-Division
Grant ID: DP2-GM-126894

Radhika Subramanian is an Assistant Professor in the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard Medical School. Her lab focuses on elucidating the fundamental principles by which intracellular spatial organization on the micron-length scale is achieved by the collective activity of nanometer-sized proteins. Radhika received her M.Sc. in Chemistry from the Indian Institute of Technology in Delhi, India. She performed her doctoral research with Dr. Jeff Gelles at Brandeis University followed by postdoctoral training in the laboratory of Dr. Tarun Kapoor at the Rockefeller University. In addition to the NIH New Innovator Award, Radhika is a Pew Biomedical Scholar and a recipient of the Smith Family Award for Excellence in Biomedical Research.

Brian Wainger, M.D., Ph.D.
Massachusetts General Hospital | Harvard Medical School

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“I’m thrilled to receive the award. It’s a great honor, and I’m grateful for the hard work of my group, particularly Joao Pereira and Anna-Claire Devlin, that enabled it. It’s also of course due to very strong support from MGH, the departments of Neurology and Anesthesia, Critical Care & Pain Medicine. And with the award comes an even greater responsibility to produce research that ultimately helps our patients – I’m excited and humbled by that.”

Project Title: A Human Stem Cell-Derived Neuromuscular Junction Model for Amyotrophic Lateral Sclerosis
Grant ID: DP2-NS-106664

Brian Wainger is a physician scientist at Massachusetts General Hospital and Assistant Professor of Neurology and Anesthesiology at Harvard Medical School. He received his undergraduate degree in molecular biology from Princeton University and M.D./Ph.D. degrees from Columbia University, where he worked on ion channel physiology with Steven Siegelbaum. Following medical residency in the Partners Neurology Program and clinical fellowship in Interventional Pain Medicine at Massachusetts General Hospital, he completed a research fellowship with Clifford Woolf at Boston Children’s Hospital and the Masters Program in Clinical and Translational Investigation at Harvard Medical School. He is a Principal Investigator at Massachusetts General Hospital, Principal Faculty at the Harvard Stem Cell Institute and a member of the Harvard Neurobiology Program. His lab research focuses on modeling motor and sensory neuron diseases using stem cell technology and electrophysiology.

Early Independence Award

The Early Independence Award supports outstanding junior scientists with the intellect, scientific creativity, drive, and maturity to flourish independently by bypassing the traditional post-doctoral training period.

Zirui Song, M.D., Ph.D.
Harvard Medical School and Massachusetts General Hospital

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“It is an honor to receive this grant and join an inspiring community of investigators. I am grateful to the faculty and colleagues who made my training possible. This grant will allow me to continue my research on strategies to improve the value of care, including studying efforts to decrease costs, improve quality, and increase the sustainability of our public programs like Medicare. In addition, this grant provides an opportunity to better understand how providers are leading delivery system reforms on the front lines and how different segments of the population are faring in the era of health care reform.”

Project Title: Inequities in Health Outcomes in the Twenty-First Century: Understanding New Causes and the Impact of Delivery System Reforms on Health Care Disparities
Grant ID: DP5-OD-024564
Funded by the National Center for Complementary and Integrative Health

Zirui Song is an assistant professor of health care policy at Harvard Medical School and an internal medicine physician at Massachusetts General Hospital. His research has focused on health care spending and quality under new payment models for provider organizations, the impact of changes in Medicare physician payment policy, and the economics of health insurance in the Medicare Advantage program. He received a B.A. in Public Health Studies with honors from Johns Hopkins University, an M.D. magna cum laude from Harvard Medical School, and a Ph.D. in Health Policy, Economics track, from Harvard University, where he was a fellow in Aging and Health Economics at the National Bureau of Economic Research. He completed his residency training at Massachusetts General Hospital.

Brain Imaging Studies Provide New Insights into Biological Basis of Behaviors in Schizophrenia and Autism

Researchers at Massachusetts General Hospital are using brain imaging technology to learn more about how individuals with autism and schizophrenia view the world through different lenses.

Imagine sitting alone in an empty movie theater. Just before the film starts, another person comes in and takes the seat right next to you, even though there are plenty of other seats available.

How would you react?

Presumably, you wouldn’t be very comfortable. It would probably be difficult to concentrate on the movie. Your fight or flight response might even kick in.

How would your reaction differ if you were in a crowded theater, and the same person took the seat next to you because it was the only one left? In that context, it seems much more reasonable.

We have similar unspoken rules about making eye contact. Too much eye contact can seem threatening or flirtatious, while too little can make the other person think you are bored or disinterested.

Most of us manage these behaviors by instinct. But what happens when the brain circuitry driving them misfires? When the simple act of making brief eye contact causes the same burning sensation as if someone is staring right at you, or when your personal space bubble becomes so enlarged that others can make you uncomfortable without realizing it?

Two researchers at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital are using brain imaging technology to gain new insights into how the brain systems that typically manage personal space and eye contact work differently in individuals with schizophrenia and autism.

Nouchine Hadjikhani, MD, PhD, and Daphne Holt, MD, PhD

Daphne Holt, MD, PhD, is exploring how perceptions of personal space differ in individuals with schizophrenia, and how these differences contribute to symptoms such as isolation and withdrawal. Nouchine Hadjikhani, MD, PhD, is studying how individuals with autism respond to eye contact, and how this can influence their behavior and social interactions. 

Their findings could revolutionize the way we understand, treat and assess those who suffer from these disorders. Continue reading “Brain Imaging Studies Provide New Insights into Biological Basis of Behaviors in Schizophrenia and Autism”

Researchers Develop a Promising New Test for Early Diagnosis of ‘Alzheimer’s of the Eye’

What would you think if words started disappearing suddenly from the books and news articles you were reading? Or you started noticing dark spots on the screen while watching a show on Netflix? Or you suddenly had difficulty recognizing faces?

While you might start thinking that your mind is playing tricks on you, in the case of age-related macular degeneration (AMD), these disorienting experiences are caused by structural damage to the eyes.

Clinicians and researchers have struggled to find a predictive measure that identifies patients at risk for developing the advanced stages of the disease.

Researchers based at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary may have identified a solution. The research team has successfully tested a new method for identifying patients with AMD by looking at specific markers in their blood.

The blood-based test has the potential to improve early diagnoses for AMD patients and may lead to more treatment options, as well as personalized, precise treatment for earlier stages of the disease.

What is Age-Related Macular Degeneration?

Known as the ‘Alzheimer’s of the eye,’ AMD affects nearly five million people across the world, and is the leading cause of blindness in people over 50 in developed nations.

The disease is caused by a buildup of yellowish lipid proteins underneath the retina, the light sensitive portion of the eye. Over time, the proteins damage the structure of the retina, which leads to the symptoms described above. By the time patients start to experience the visual degradation that accompanies AMD, the damage is already done.

Finding a Method for Diagnosis

To test out their new method for diagnosing AMD, scientists took blood samples from 90 participants with varying degrees of AMD, including early, intermediate and late-stage cases. These samples were then compared to 30 individuals who do not have AMD.

Researchers used a new technique known as “metabolomics,” — the study of tiny particles called metabolites in the body that reflect our genes and environment.

Their analysis revealed 87 metabolites that were significantly different between subjects with AMD and those without. The team also noted varying characteristics between the blood profiles of each stage of disease.

Out of the 87 molecules identified, the majority were found to be lipids, which have long been a point of interest in AMD research.

“Because the signs and symptoms of early stage AMD are very subtle, with visual symptoms only becoming apparent at more advanced stages of the disease, identification of [lipid] biomarkers in human blood plasma may allow us to better understand the early to intermediate stages of AMD so we may intervene sooner, and ultimately provide better care,” said co-senior author Joan W. Miller, M.D., Chief of Ophthalmology at Massachusetts General Hospital and Mass Eye and Ear.

Preventative Measures

More research needs to be done before the blood tests are available in the clinic. For now, the best way to monitor patients for signs of AMD is by conducting regular eye tests after the age of 45.

Given that risk factors for AMD include being overweight, having high blood pressure and smoking or drinking alcohol to excess, it may be possible to reduce your risk by making healthy lifestyle choices, including:

  • Maintaining a healthy weight
  • Eating lots of green leafy vegetables and fish
  • Quitting smoking
  • Managing your blood pressure

Find more information on AMD on the National Eye Institute website.

The Research Institute:
Saving Lives Through Science

Did you know the Massachusetts General Hospital Research Institute is home to the largest hospital-based research enterprise in the United States?

Learn more about the Research Institute on our website.

Study Finds Less than 20% of Americans are Active Consumers of Science News

Here at the Mass General Research Institute, we live and breathe science news every day.

We’re eager to find out what’s happening in the research labs, centers and institutes at Massachusetts General Hospital (and with biomedical science in general), and share what we’ve learned on our blog and website.

But what about the general public? Do they share the same interest in science?

A recent Pew Research Survey of 4,000 adults aged 18 and over found that only 17 percent of respondents were “active consumers” of science news. Active consumers were defined as those who get science news several times a week, either by chancing across it or by actively seeking it out.

Details of the Study

The study found that general news outlets are the most common sources of science stories, though respondents indicated that they tend to view information from niche sources such as scientific institutions, museums, documentaries and science-specific magazines as more accurate.

More than 80 percent of those who follow science news cited curiosity as their prime motivating factor. Other reasons cited by respondents for following science news was that the information helps them make decisions in their everyday lives, and that they enjoy talking about science with others.

There is also a family connection—many of the respondents who were parents said that they sought out science news due to the activities and interests of their children.

When it comes to the coverage of science itself, some respondents criticized science journalists for too much emphasis on “gee-whiz” writing that doesn’t do enough to explain the relevance of the science for the average person, or assess the quality of the research.

Some 44% of survey respondents said it was a “big problem” that the public doesn’t know enough about science to understand research findings in the news. A similar number of respondents said that with so many studies being published, it can be difficult to distinguish between high and low quality work.

Finding Meaning in the Results

So what does that mean for researchers and the research communications team at Massachusetts General Hospital?

We have an opportunity to be a trusted and accessible voice for science. We can take a hard look at the way we communicate our findings to see if we are using too much jargon, failing to explain key concepts or not taking the time to explain how our work could impact human health down the road—even if the potential benefits are a long way off.

In an era where hot button issues such as climate change and childhood vaccinations have scientists facing an increasing level of scrutiny, it’s important that we continuously work on improving our communication skills.

Communicating Science at Mass General

Through the Office of the Scientific Director, the Mass General Research Institute has launched several programs designed to improve the way our researchers talk about science.

We have organized communicating science competitions at HUBweek and the Cambridge Science Festival, and hosted workshops on science communication in conjunction with the Alan Alda Center For Science Communication.

We also share tips on communicating science on our Facebook and Twitter pages. Here are a few resources to get you started:

Science is a complex and ever-changing field. Each new advance, from personalized medicine to CRISPR gene editing, creates a new set of terminology that might make perfect sense to the research community, but is totally unknown to the general public.

By challenging ourselves to be better communicators, we can advocate for the importance of medical research and its potential to improve the lives of patients, both here at Mass General and across the globe.

The Research Institute:
Saving Lives Through Science

The Massachusetts General Hospital Research Institute is the largest hospital-based research program in the United States, with a community of over 10,000 people working across more than 30 institutes, centers and departments.Our researchers work side-by-side with physicians to pioneer the latest scientific advancements for curing disease and healing patients in Boston, across the United States and around the world.To learn more about the Research Institute, please visit our website.