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Translational Research: Turning Patient Observations and Laboratory Findings into Clinical Trials

The Translational Research Program is dedicated to developing clinical trials for people living with a brain and spine tumor—which takes a considerable amount of research in a laboratory and patient observations in the clinic.

By Neuro-Oncology Branch Staff

September 28, 2021

 

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Dr. Jing Wu in the Clinic

Developing clinical trials for people living with a brain and spine tumor is no easy feat. It takes a considerable amount of research in a laboratory and patient observations in the clinic to develop new ways to treat the disease and improve outcomes. The Translational Research Program at NCI’s Center for Cancer Research (CCR), Neuro-Oncology Branch (NOB) is dedicated to doing just that.

The Translational Research Program is led by Lasker Clinical Research Scholar and Investigator Jing Wu, M.D., Ph.D. Dr. Wu received her medical degree from Capital Medical University in Beijing, China and her Ph.D. in neuroscience from the University of Texas Medical Branch at Galveston. She then completed a neurology residency at University of Texas at Houston and a subspecialty fellowship in neuro-oncology at University of Texas MD Anderson Cancer Center. With training in both basic science research and clinical research, Dr. Wu realized that researchers can make a great difference in the field. This motivated her to pursue translational research, combining both clinical and laboratory research.  

Using Clinic Observations to Improve Research and Care

Translational research is the process of taking scientific discoveries made in the laboratory to the clinic, so researchers can observe how patients respond to a new treatment developed based on the laboratory findings. Then when more clinical observations are made, they are once again taken back to the laboratory. This interactive process allows investigators to study a focused clinical question in a laboratory where they can safely test hypotheses in pre-clinical models before testing on people.

Dr. Wu’s approach to translational research starts with patient care. This helps her pick a research topic, and then based on her readings, understandings, and observations from her clinical practice she picks a focused clinical question to study. “I will take that question to the laboratory and investigate it in preclinical models. By testing the question in brain tumor models, we can better understand what we saw in the clinic by conducting a study in the laboratory,” says Dr. Wu. Once she has a laboratory finding, Dr. Wu and her team test their hypothesis through a clinical trial with brain and spine tumor patients and continue to make further observations.

Translational research is a “back and forth process, not a one-way trip,” says Dr. Wu. “You have to go back and forth frequently to better understand the disease. This process helps us understand why some patients might respond better to a specific treatment than others, leading to precision medicine.”

Translational Research Program

Dr. Wu’s Translational Research Program focuses on developing brain and spine cancer clinical trials that are based on preclinical studies. Her goal is to identify and address important clinical problems or barriers to progress in neuro-oncology to ultimately improve scientific knowledge and clinical practice.

Dr. Wu finds that translational research is especially important due to the uniqueness of tumors in the brain and spinal cord compared to other organs. “Understanding both the clinical and laboratory parts of neuro-oncology helps me to develop focused research projects that lead to clinically relevant results that guide clinical practice,” shares Dr. Wu.

The Translational Research Program works closely with the Radiation Oncology Branch and Molecular Imaging Branch at the CCR and the National Institute of Mental Health at NIH to translate preclinical models and imaging biomarkers into clinical trials. Dr. Wu’s laboratory uses metabolic imaging to monitor patients with brain and spine tumors in order to capture when the disease progresses. More specifically, Dr. Wu’s laboratory investigates why and how tumors become malignant (cancerous) in a subset of patients with IDH-mutated gliomas. Because this transformation is a process that cannot be mimicked or created in a laboratory setting, Dr. Wu’s team monitors patients closely in the clinic with metabolic imaging with the goal to capture when a tumor might be transforming to a higher grade. This clinical imaging technology allows Dr. Wu to capture a window of opportunity to obtain tumor tissue and further investigate this in her lab. “This clinical trial program creates the opportunity to answer important questions to potentially understand what causes tumor transformations so they can be detected early and intervened, turning the slow progression into a chronic state,” explains Dr. Wu.

A recent accomplishment of Dr. Wu’s program was a successful phase 1 trial with the novel target agent zotiraciclib plus temozolomide for the treatment of recurrent anaplastic astrocytoma and glioblastoma. 

Through a very thorough preclinical study, Dr. Wu’s team was able to introduce a drug, that had never been tested before in patients with brain tumors, for use in patients with glioma. Gliomas comprise about 30 percent of all brain and central nervous system tumors and 80 percent of all cancerous brain tumors. As a result, the drug was given orphan drug designation by the U.S. Food and Drug Administration.

During this early phase clinical trial, a subset of patients had a better response to the experimental therapy. This led to ongoing research to confirm the findings in the preclinical models and explain the underlying mechanisms in the laboratory. Dr. Wu’s team is actively working with Mark Gilbert, M.D., NOB Branch Chief, to open the phase II study of zotiraciclib plus temozolomide versus temozolomide alone in recurrent high grade glioma patients through the Brain Tumor Trials Collaborative.

Dr. Wu credits her success to strong mentorship and collaboration throughout her career. With the help of her hard working, supportive and passionate team in the clinic and laboratory Dr. Wu feels confident that they will make a difference in the field. “At the end of the day, we only have one goal, for our brain tumor patients to live longer with a good quality of life,” shares Dr. Wu.

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