Postdoc Profile: Nabi M. Nurunnabi, PhD


Md “Nabi” Nurunnabi, PhD, is a postdoctoral research fellow at the Massachusetts General Hospital Center for Systems Biology (CSB) and the Cardiovascular Research Center (CVRC). He is also Chair of MGH Postdoc Association (MGPA).

He is biomedical scientist with education and training in both academia and industry as pharmacist, chemist, and bioengineer. He is working on the design and development of target-specific therapeutic approaches for various diseases such as cancer, diabetes, fibrosis, and cardiovascular (stroke and myocardial infarction) along with immunology.

He is working in Jason McCarthy’s group in the Center for Systems Biology at Massachusetts General Hospital.

This interview was conducted by Mojtaba Moharrer, PhD, a communications intern with the Mass General Research Institute.

What is your field of research?

We call our field of research nanomedicine. We use nanotechnology, or a nanoengineering approach, to design and develop targeted therapeutic delivery systems.

In most cases, the conventional method of therapeutic delivery (such as administering a drug orally or intravenously) is not targeted. As a result, the therapeutic molecule is randomly distributed throughout the body by the circulatory system and can localize in any part of the body—not necessarily where you want it to.

This can both increase the cost of treatment and the potential for toxicity, because you have to give the patient a higher dose to get required therapeutic effect.

Our approach is to actively direct the therapeutics (small molecules or large biologics) to specific target sites in the body. We also tag therapeutics with imaging agents so we can detect and monitor the location of the therapeutics after administration.

We are also using nanotechnology for disease detection and diagnosis. Early detection and diagnosis helps to reduce treatment costs and increase survival rates, especially with a disease like cancer.

What research projects are you working on?

On the diagnostic side, I have been working to develop a single nano-probe for non-invasively detecting cancer at earlier stages than traditional screening and diagnostic tools.

For targeted therapeutics, I have been searching for convenient and unique materials that will be stable, ultra-small (within few nanometers), biocompatible and cost-effective.

Part of my goal is to translate the small or large molecular therapeutics for oral delivery, as the oral dosage form has a large market that is of great interest to biopharmaceutical companies.

In this regard, I have developed a platform technology that is highly feasible for oral delivery of anticancer drugs. I have also developed technology that can be used for oral delivery of large molecules such as Glucagon-Like Peptide 1 (GLP-1) and antigen (PR8), which are highly effective for diabetes therapy and immunology, respectively. Both technologies have been patented and have generated interest from industry.

The advantages of these delivery systems is that they shield the therapeutics and protect them from harsh environment of stomach, enhance absorption through small intestinal membrane and deliver the therapeutic to the site of action.

They are also helpful for controlling the release profile of the therapeutics to reduce dosage frequency.

My current research focuses on imaging and treatment of cardiovascular disease and fibrosis. Fibrosis is a disease caused by cell inflammation, which results in the formation of collagen (also known as fibrin) on the extracellular matrix.

Chemotherapy treatments can trigger fibrosis in the cells that line the blood vessels and coronary arteries. Secretions of excess collagen from these cells can cause a complete or partial blockage of the vessel or artery, which can in turn cause hypertension and/or cardiac arrest.

We are trying to develop a nano-probe composed of therapeutic molecule, targeting peptide, and imaging contrast agent for simultaneous diagnosis and treatment of the fibrosis.

We are also developing a particulate tissue plasminogen delivery system that is designed to target and bind to the blood clot and destroy it in vivo. This approach could help prevent the hemorrhaging and nonspecific toxicity that can result from conventional plasminogen-mediated stroke therapy.

What are your hobbies outside of the lab?

I would say reading. I try to read everything that interests me, not just academic books or research articles. I like to spend the rest of my time with family, visiting zoos and gardens or walking together. I really enjoy chatting with friends and colleagues. I try not to miss any opportunity to make new friends. Who knows? Anyone that I meet could be a potential research collaborator in the future.

I always carry the book “The Magic of Thinking Big” with me and have been reading it again and again since 2013. I read couple of pages when I feel a lack of motivation or inspiration.

What have been the most valuable academic and non-academic lessons you learned during your postdoctoral fellowship?

Academic lesson: Actively seek out collaborators who have expertise in areas that you don’t. Non-academic lesson: Be expressive, open for networking and idea sharing.

Weekend Links

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photo courtesy of Perimeter Institute 

We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Vanishing Bone: The Medical Mystery That Could Have Derailed Millions Of Hip Replacements – The twist-filled backstory of disaster averted as told by former Mass General chief of joint replacement surgery Dr. William H. Harris

Standard Age For Mammograms Puts Nonwhite Women At Risk, Study Finds – New research from Mass General’s Dr. David Chang finds that current guidelines recommending mammograms beginning at age 50 were developed based on the majority population and may not be applicable to minority women. The results highlight the need to respect racial differences at the scientific research stage in order to improve delivery of clinical care.

Pediatricians Call For Universal Depression Screening For Teens – The American Academy of Pediatrics recently issued updated guidelines that call for universal screening for depression. How do experts think this will help the growing mental health problem among teens?

Forces of nature: great women who changed science – Celebrating the many fundamental discoveries made by women who pursued their research in the face of gender discrimination and did not get the recognition they deserved (plus a free collection of print-at-home posters of these remarkable women!)

Scientists show how the brain may be wired for drinking fluids – How do our bodies know when we’ve quenched our thirst and have had enough water? An NIH-funded study of mice provides a detailed diagram of the brain circuits behind thirst and satiety.

These scientific images are both research tools and works of art – In acknowledgement of science’s visual underpinnings, the Massachusetts Institute of Technology’s Koch Institute has for the past eight years featured a public gallery of science images in its Cambridge, Mass., lobby. Here’s a look at this year’s 10 winners.

Research Awards and Honors: February 2018

February 2018 awards honors.pngMassachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

Dania DayeDania Daye, MD, PhD, a resident in the Department of Radiology, has received a Trainee Research Prize from the Radiological Society of North America in the health services policy and research category, for her research “Point of care virtual radiology consultants in primary care: A new model for patient-centered radiology.”

“This award highlights the importance of the emerging research in patient-centered care models in radiology and will further promote my efforts in this field. I was very humbled to have been chosen to receive the award. It will certainly have a positive impact on my career trajectory moving forward.” 


Leif Ellisen, MD, PhD, program director for Breast Medical Oncology at the MGH Cancer Center and Weissman Family MGH Research Scholar, and Srinivas Vinod Saladi, PhD, instructor in the MGH Cancer Center, have received the Douglass Foundation Prize for Excellence in Hematology-Oncology Laboratory Research. This award honors their research published in the journal Cancer Cell. The award is given annually recognizing the excellent scientific publication from the cancer center. Pictured from left, Nicholas Dyson, PhD, scientific director of the MGH Cancer Center; Saladi and Ellisen

“We were truly honored to receive the Douglass Family Foundation award recognizing excellence in research at the MGH Cancer Center. As a clinician-scientist, it is very rewarding to be recognized for work that yields new insights into the basic biology of cancer. It is also humbling to be singled out among all my brilliant investigator colleagues in our Cancer Center for recognition. This award is a tribute to the hard work of the lab members, and it encourages us all to strive for excellence in scientific discovery and clinical application.”

Shyamala-Maheswaran.jpgShyamala Maheswaran, PhD, associate professor and scientific director of the MGH Center for Cancer Risk Assessment, has received an Outstanding Scientist Award from the American Association of Indian Scientists in Cancer Research (AAISCR). This award recognizes outstanding, novel and significant biomedical research which has led to important contributions to the fields of basic cancer research, translational cancer research, cancer diagnosis, prevention of cancer or treatment of cancer patients. The award will be presented at the AAISCR meeting in Chicago, Illinois on April 16.

“I feel honored and happy to receive the Outstanding Scientist Award from the American Association of Indian Scientists in Cancer Research.  Important contributions to a field are never possible without the effort of a talented research team. I have been very fortunate to work with remarkable scientists, postdoctoral fellows, students and research technicians, so this award belongs to all of us.  It gives me the impetus to continue to be more productive and answer critical questions that will make a difference in the field of basic and translational cancer research.” 


Raul Mostoslavsky, MD, PhD, The Laurel Schwartz Associate Professor in the MGH Cancer Center and The Kristine and Bob Higgins MGH Research Scholar, has received the Premio Raices (Roots Prize) from the Ministry of Science and Technology in Argentina. The prize recognizes Argentinian scientists abroad for their achievements and continued collaborations with scientists in Argentina.

“I was truly moved when I heard I received this award (and happy to know that my parents, who attended the award ceremony, will be proud!). We, as scientists, work tirelessly for the sake of understanding nature, for the possibility of discovery something new, with the hope that one day, one of these discoveries may benefit a patient. Not for awards. But receiving a recognition like this made me feel that I’m contributing my grain of sand to advance science, that I may be doing something right, and for this I was both flattered and thankful.”

Sabrina Paganoni.jpgSabrina Paganoni, MD, PhD, of the Department of Physical Medicine and Rehabilitation, has received the 2017 Clinician Scientist Development Three-Year Award in ALS sponsored by the American Academy of Neurology and the American Brain Foundation. Paganoni is nationally recognized as a leader in cutting-edge research in ALS. Throughout the past three years, she has obtained funding to conduct four Phase 2 clinical trials for ALS. These trials include promising biomarkers to measure target engagement of various compounds in patients with ALS.

“This Career Development Award comes at a critical time in my career when I am starting new projects, generating data, and applying for funding to become an established investigator with expertise in ALS clinical research. This award will allow me to dedicate the next few years to ALS clinical trials, while still continuing to see ALS patients in the clinic.”

12 Days of Research at Mass General: A Strategy for Sneaking Drugs Into Tumor Cells

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

July 2017:

Could a Technique Echoing an Ancient Greek Military Strategy Point the Way to More Effective Cancer Treatments?

Trojan horse

According to Greek legend, the Trojan horse was a wooden structure built by Greek soldiers and presented to the Trojans as a gift after a long and fruitless siege of the city during the Trojan War. When the Trojans brought the gift horse within their city walls, the Greek soldiers who were hidden inside crept out under the cover of night and launched a deadly surprise attack. Historians continue to debate how much of the tale is based in fact and how much in myth.

At Massachusetts General Hospital, a real-life Trojan horse scenario that takes place on the nanoscale level could provide a way to sneak cancer drugs into fortified tumor cells so the drugs can attack from within.

Here are five things to know about a new study from the Mass General Center for Systems Biology:

1. Think of nanoparticles as the Trojan horses of cancer therapy. These tiny molecules (typically between 20 and 100 nanometers in size) are increasingly being used to transport drugs to a specific target in the body. The ability that researchers have to easily change the size and surface characteristics of the nanoparticles and control the time and location of the drug’s release makes them ideal for drug delivery systems.

2. Nanoparticles are small enough to carry the drugs (the Greek soldiers) through the body and can protect the encapsulated drug from toxic substances in the bloodstream that are used in infusion chemotherapy. However, in clinical practice, getting these nanoencapsulated drugs into patients’ tumors has been challenging—tumor blood vessels are difficult to break through, which limits the passage of any drugs from the bloodstream into tumor cells. Although it’s usually beneficial for blood vessels to maintain barrier function, their tough exteriors are a disadvantage in cancer therapies.

3. A 2015 study by Miles Miller, PhD, of the Center for Systems Biology, and his colleagues showed that tumor-associated macrophages — immune cells found around tumors that are in charge of engulfing pathogens, foreign materials and dead cells — can improve delivery of nanoparticle-based therapies to tumor cells. They also found that radiation therapy made it easier for substances to pass through tumor blood vessels. But exactly how these effects are produced and how they could be combined to enhance nanomedicine delivery was not known. Answering those questions was the goal of the current study.

4. Miller and his team found that macrophages can be prompted to act like Trojans, helping to bring the drugs inside the tumor, if the tumors are treated with radiation prior to administering the drugs. In the same way that a siege weakens the resistance of a city, the radiation weakens the blood vessels within the tumor. It also increases the number of macrophages attracted to tumor blood vessels which, in turn, pick up the drug-laden nanoparticles and bring them into the tumor. The sudden influx of macrophages into the weakened walls of the blood vessels causes many of the vessels to burst, thus flooding the tumor cells with the drug-laden nanoparticles and improving drug delivery by 600 percent.

5. “Finding that this combination of radiation and nanomedicine leads to synergistic tumor eradication in the laboratory provides motivation for clinical trials that combine tumor rewiring using radiation therapy with nanomedicine,” says Miller, who was lead author of the study. “Most of the treatments and nanomedicines employed in this study are FDA approved for cancer treatment, so this combination treatment strategy could be tested in clinical trials relatively quickly.”

Radiation & Macrophages

Ralph Weissleder, MD, PhD, Director of the MGH Center for Systems Biology is senior author of the Science Translational Medicine paper.

You can find the original post here.

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12 Days of Research at Mass General: Aspirin and Risk of Cancer Death

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

April 2017:

New Study Finds Low-Dose Aspirin May Lower Risk of Cancer Death

63889039 - heap of round white tablets and plastic pills bottlenew study from Massachusetts General Hospital reports that long-term regular aspirin was associated with a lower risk of dying from various types of cancers.

Lead author, Yin Cao, MPH, ScD, a researcher in the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, and her team studied the health outcomes of approximately 86,000 women and 44,000 men who had been prescribed aspirin at various doses and duration over the course of 32 years.

The biggest benefit came from reducing colorectal cancer deaths: Men and women who regularly took aspirin reduced their chances of dying from colorectal cancer by a third. Women also reduced their risk of dying from breast cancer by 11 percent, while men were 23 percent less likely to die from prostate cancer. The benefit seemed to be greatest for people taking two to seven doses of regular-strength aspirin—325 mg per tablet—each week.

It’s still not entirely clear how aspirin lowers cancer risk. Researchers suspect that aspirin’s ability to lower inflammation and control inflammatory factors that may contribute to abnormal cell growth in tumors may reduce risk. Plus, its anticoagulant properties that prevent clots from forming may prevent cancerous cells that break away from tumors from sticking to other areas in the body and growing into metastatic tumors.

Regular aspirin use has already been recommended as a preventative measure against cardiovascular disease and colorectal cancer.

Cao cautions that patients and physicians should consider all potential benefits and risks before beginning any new aspirin regimens. More work is needed to weigh these potential benefits against the risks of long-term use, which include gastrointestinal bleeding and hemorrhagic stroke.

The data of this study was presented at the American Association for Cancer Research Annual Meeting 2017, which took place earlier this month in Washington, DC.

You can find the original post here.

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Weekend Links


We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Crowdsourcing Cancer Research – Researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital will be recruiting attendees at the annual Radiological Society of North America meeting next week to help them label tumors from an archive of images from the Cancer Imaging Archive. Once the tumors are identified, the images will help create new machine-learning based tool cancer diagnoses and prognosis.

Looking Back: Mass General and the Coconut Grove Fire – This Proto podcast talks about the role Mass General played in treating victims of the deadly Cocoanut Grove fire in Boston in 1942, in which 492 people died. The podcast features the story of a survivor who was treated at Mass General and an interview with surgeon John Schulz on how the fire led to innovations in burn care.

Study finds that 1 in 5 show symptoms of PTSD after cancer diagnosis – Roughly 1 in 5 cancer patients developed post-traumatic stress disorder within six months of their diagnosis—and a small percentage still experienced trauma-related symptoms six months later, according to new research in the journal Cancer. The study was conducted by a research team that included investigators from Boston (the Dana Farber Cancer Institute) and Malaysia.

Science in the House: A Live DJ/VJ experience inspired by particle physics – Check out highlights of a two performances from the Manchester Science Festival that combine electronic dance music with science themed visuals.

Top photo courtesy of the Martinos Center for Biomedical Imaging

Researchers Use Machine Learning to Improve Breast Cancer Screening Techniques

Imagine enduring a painful, expensive and scar-inducing surgery—only to find out afterwards that it wasn’t necessary.

This is the situation for many women with high-risk breast lesions—areas of tissue that appear suspicious on a mammogram and have abnormal but not cancerous cells when tested by needle biopsy. Following surgical removal, 90% of these lesions end up being benign.

A change in the standard of care could be on the horizon thanks to researchers at Massachusetts General Hospital and MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) who have found a more precise and less invasive way to separate harmful lesions from benign ones.

From left: Manisha Bahl, director of the Massachusetts General Hospital Breast Imaging Fellowship Program; MIT Professor Regina Barzilay; and Constance Lehman, chief of the Breast Imaging Division at MGH’s Department of Radiology. Photo courtesy of MIT News

“The decision about whether or not to proceed to surgery is challenging, and the tendency is to aggressively treat these lesions [and remove them],” said Manisha Bahl, MD, Director of the Breast Imaging Fellowship Program at Mass General, in a recent interview.

Bahl, along with a team of researchers, have harnessed the power of artificial intelligence (AI) to develop a more accurate and less invasive screening method for high-risk lesions. When tested, the machine correctly diagnosed 97 percent of 335 high-risk breast lesions as malignant and reduced the number of benign surgeries by more than 30 percent compared to existing approaches. These results were recently published in Radiology.

The team developed an AI system that uses machine learning to distinguish between high-risk lesions that need to be surgically removed from those that should just be watched over time. They created this model by feeding it data on over 600 high-risk lesions, including information on the patient’s demographics and pathology reports, and then tasked it to identify patterns among the different data elements.

Through a process called deep learning, the machine uses the data to create an algorithm that can be used to predict which high-risk lesions should be surgically removed. This process differs from traditional software programming in that the researchers did not give the machine the formula for diagnosis, but rather let it analyze the data and identify patterns on its own.

“To our knowledge, this is the first study to apply machine learning to the task of distinguishing high-risk lesions that need surgery from those that don’t,” said collaborator Constance Lehman, MD, PhD, chief of the Breast Imaging Division at Mass General’s Department of Radiology, in a recent interview. “We believe this could support women to make more informed decisions about their treatment and that we could provide more targeted approaches to health care in general.”

Lehman says Mass General radiologists will begin incorporating the model into their clinical practice over the next year.

Could the Microbiome be the Key to Ending Chemotherapy-Induced Pain?


Most of us have experienced the odd sensation of “pins and needles” in our hands or feet. While annoying and painful, the sensation usually goes away quickly.

But for many people with peripheral neuropathy, a disorder involving increased sensitivity of nerves outside of the brain and spinal cord, this experience may linger for months to years.

“It’s a horrible condition,” said Shiqian Shen, MD, clinical investigator in the Massachusetts General Hospital Center for Translational Pain Research and director of the Mass General TelePain Program. “You literally want to shake off your leg, but you can’t.”

Unfortunately, a third of cancer patients who receive chemotherapy encounter this as a side effect, a condition known as chemotherapy-induced peripheral neuropathy (CIPN). This neuropathy is a result of nerve damage or impairment of the nervous system and often is chronic. If the pain is severe enough, chemotherapy dosages must be lowered, which causes the treatment to be less effective.

With the survival rates for many cancers increasing due to the improved understanding of genetic mutations, targeted therapies and immunotherapy, CIPN has become a major challenge and can hurt a survivor’s quality of life.

Dr. Shen and Jianren Mao, MD, PhD, chief of the Mass General Pain Management Center and vice chair for research in the Department of Anesthesia, Critical Care and Pain Medicine, are leading a research team in exploring why patients undergoing chemotherapy develop CIPN.

There is strong evidence that the gut, which carries about 10 trillion bacteria, has a major impact on the central nervous system. Previous research in the field has also shown that gut microbiota plays a critical role in the tumor-killing effect of many chemotherapeutics drugs. In a recent study published in Nature Neuroscience, the researchers questioned whether an immune response that results from interactions between chemotherapy drugs and the bacteria in the microbiome also plays a role in developing CIPN.

The researchers exposed two sets of mice, one with a normal microbiome and one that had their microbiome essentially eliminated through antibiotic treatments or genetic engineering, to oxaliplatin—a chemotherapy drug used to treat colon or rectal cancer and that is known to cause CIPN. The normal mice manifested symptoms of CIPN while those without a microbiome did not. Therefore, a microbiome is necessary for CIPN symptoms to manifest.

Next, the team dug into why the microbiome influences the onset of CIPN.

The researchers determined that the mice who experienced CIPN had higher levels of two proteins involved in inflammation (IL-6 and TNFalpha) in the dorsal root ganglia (DRG). This inflammatory response in the DRG leads to an increase in neuron sensitivity, which is what causes the neuropathy pain and tingling in a person’s extremities.

The team found further evidence that suggests a reaction between the chemotherapy agent and bacteria in the microbiome, releases lipopolysaccharides (LPS), a molecule found in bacteria on the gut lining, into the bloodstream. LPS then appears to cause a chain reaction that increases the levels of the two inflammatory proteins in the DRG.

“We found there’s a concurrent response—one initiated by the chemotherapy agent, and one by the inflammatory response,” said Shen. “They work hand in hand to promote the pain.”

However, there is a dilemma to sort out. Previous research has found that chemotherapy treatments such as oxaliplatin and cyclophosphamide are dependent on the gut microbiome. Meaning chemotherapy does not work well without help from a normal microbiome, but having it runs the risk of developing CIPN.

“Our research has revealed that you cannot get rid of the gut microbiome entirely to prevent side-effects because your therapeutic effect is also linked to the same presence,” says Shen.

The researchers are conducting follow-up studies to see if the same results are found in humans, and to see whether the same phenomenon exists in other type of neuropathic pain.

Potential in the Clinic

Since eliminating a cancer patient’s microbiome will essentially render chemotherapy treatment ineffective, more research will need to be done to see if investigators can determine if and how an individual’s microbiome composition affects their likelihood of developing CIPN. If they can identify favorable bacteria profiles, clinicians may be able to reduce the risk of developing CIPN by prescribing probiotics or fecal transplants in advance of starting chemotherapy. On the flipside, knowing the optimal microbiome profile that reduces risk of CIPN for every chemotherapy agent may help oncologists select the ideal chemotherapy drug for each patient.

Weekend Links


We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Creative Minds: A New Way to Look at Cancer

Better Patient-Provider Communication Needed for Obesity Care

Eugenics 2.0: We’re at the Dawn of Choosing Embryos by Health, Height, and More

6 Speaking Tips for Scientists and Engineers (editor’s note: Melissa Marshall, featured in this article, recently spoke to Mass General clinicians about how to effectively present scientific work. We were so impressed by her talk that we wanted to introduce her to our readers) 

Looking for a great book for the young scientist in your life? The long list of 2018 AAAS/Subaru SB&F (Science Books and Films) Prize winners for Excellence in Science Books has been released. Prizes are awarded each year in the following categories:

  • Children’s Science Picture Books
  • Middle Grade Science Books
  • Young Adult Science Books
  • Hands on Science Books

See the full list here


Top photo: courtesy of Tim Lahan, MIT Technology Review

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.”