Ask the Expert

Innovations in Clinical Diagnostics

Brian Nahed, MD, talks to contributing editor Tanuja Koppal, PhD, about the need to develop techniques to detect and monitor disease progression

Tanuja Koppal, PhD

Brian Nahed, MD, neurosurgeon and associate professor at Massachusetts General Hospital–Harvard Medical School, talks to contributing editor Tanuja Koppal, PhD, about the need to develop techniques to detect and monitor disease progression and patient response to therapy, which will ultimately pave the way for personalized medicine. His work developing noninvasive testing for brain tumors is one such example of real-time monitoring leading to better patient treatment and care.

Q: What are some of the limitations of or gaps in existing assays and tools for clinical diagnostics?

A: While sophisticated techniques such as magnetic resonance imaging— MRI—can identify a suspected brain tumor, patients must undergo surgery to provide a tissue diagnosis and ultimately have their tumors characterized. Based on this diagnosis, clinicians then target specific therapy to a patient’s mutational characteristics. However, this information is available only after obtaining the tissue, which requires surgery and can be done only one or two times during the course of the disease. This is further compounded by the fact that patients subsequently undergo chemotherapy and radiation therapy, which can change the mutational characteristics of the tumor. Imaging cannot identify the subtle but important changes in tumor biology resulting from the therapy, creating a gap in our ability to detect real-time changes in the tumor. As a result, our therapies can only be targeted based on the characteristics of the tissue obtained from the last surgical biopsy.

Q: What are some of the things being done to overcome those limitations, and how is technology helping?

A: Brain tumor research is rapidly evolving, reflecting all of the efforts being made by clinicians and scientists to improve our understanding, treatment, and care of patients. Clinically, advances in neuroimaging have led to more detailed characterization of tumors through spectroscopy and other MRI techniques to not only define the heterogeneity of tumors but also possibly identify metabolites and potential mutational differences among brain tumors. Advances in brain tumor pathology have led to a more detailed and specific characterization of a patient’s tumor, which has given clinicians the ability to target therapy to an individual, and it has offered researchers the ability to better differentiate and analyze brain tumors between patients. The World Health Organization classification recently changed to reflect this new, detailed, and sophisticated way to diagnose and distinguish brain tumors, which will undoubtedly lead to a better understanding of how brain tumors can be treated. Advances in neuro-oncology and radiation oncology have led to patient-specific targeted therapy. In addition, clinical trials in both chemotherapy and radiation therapy have great promise to improve the treatment and survival of patients.

Q: Can you describe some of the work that you are doing to offer noninvasive options for clinical diagnosis of cancer patients?

A: Dr. Shannon Stott and I are developing the first blood-based test for brain tumors, which can capture circulating tumor cells—CTCs—and extracellular vesicles—EVs—and characterize them for molecular and genetic changes in real time. We hope to provide clinicians with a minimally invasive test that can characterize a patient’s tumor in real time throughout the duration of the disease, opening the door to more accurate detection of treatment response and hopefully identifying new mutations to target and improve the care of our patients.

Q: Can you highlight the need for innovation in biomarker discovery and clinical diagnostics?

A: Given the rapid identification of biomarkers in cancer, there is an incredible amount of interest in using a liquid biopsy to provide never-before-available access to biomarkers in blood, cerebrospinal fluid, and urine throughout a patient’s disease course. Clinically, there is a need for critical analysis of a patient’s tumor as it’s being treated in real time, particularly, as mutations change with therapy. Liquid biopsy has the potential to provide the real-time analysis of a patient’s brain tumor as it responds to therapy. There is no doubt that innovative measures to diagnose, detect, and monitor disease will be the catalyst for better and more personalized therapies.

Q: What advice or feedback do you have for researchers working to develop new diagnostics for monitoring and detecting various medical conditions?

A: There is a tremendous need for minimally invasive, real-time tests to accurately monitor and detect diseases and treatment response. As new biomarkers and mutations are identified, it is paramount that any new diagnostic tool is able to detect small changes and can do so in a manner that would be clinically relevant and feasible. There is a great deal of potential in liquid biopsies; however, there can be significant hurdles in the laboratory as one transitions a success in the laboratory into the clinical setting. Strong clinical and scientific collaborations are essential when a clinical need is identified, a project established, and ultimately products are tested and approved for clinical use, all with the goal to advance the care of our patients using targeted, more specific patient data to drive decisions. That is the hope for developing liquid biopsies.

Dr. Brian Nahed is a neurosurgeon specializing in brain tumors (glioblastoma, low-grade and high-grade gliomas, metastatic brain tumors, and meningiomas) as well as spinal disorders. Dr. Nahed attended UCLA, where he majored in neuroscience, and he attended the Yale School of Medicine. Dr. Nahed completed his internship and neurosurgery residency at Massachusetts General Hospital, where he also completed a postdoctoral fellowship with Drs. Daniel Haber and Shyamala Maheswaran in the MGH Cancer Center. Dr. Nahed was recruited to the MGH Department of Neurosurgery and the Stephen E. and Catherine Pappas Center for Neuro-Oncology in 2011. He is an associate professor at Harvard Medical School, and his research, done with his coprincipal investigator, Dr. Shannon Stott, focuses on developing the first blood-based test to diagnose and monitor brain tumors.