He didn’t know the first thing about research when he was a freshman at BYU. Now, Dr. Bob Carter oversees brain tumor research at a university hospital and makes strides in brain cancer treatment.
Carter has worked on methods to improve brain cancer diagnosis, treatment, and surgery since his early days as a neurosurgery resident at Massachusetts General Hospital (Mass General). His work as an undergraduate with BYU biochemistry professor John Mangum gave him a love for research and its ability to discover new knowledge that can benefit the medical field. He graduated from BYU in chemistry in 1986 and was accepted into an MD/PhD program at Johns Hopkins.
Johns Hopkins was at the forefront of understanding the genetic underpinnings of cancer when Carter attended in the late 1980s. Carter’s work with cancer genetics led him to Mass General and Harvard Medical School for neurosurgery residency. He stayed at Mass General for eighteen years, including his seven-year residency.
Carter chose to specialize in brain cancer because of the challenges it presents. Most brain cancer patients live only fifteen to twenty months after diagnosis. The cancer tends to spread throughout the brain, and it is difficult to find and remove every cancer cell from critical brain areas.
“If a tumor forms in the right frontal lobe, over a period of a year or two some of the microscopic tumor cells will cross to the other side, or these cells may migrate farther away from that original site. Even if you go and remove the tumor with surgery, the truth is there is always some microscopic disease that is left behind,” Carter said.
By performing surgery to reduce residual microscopic cancer cells to a bare minimum, it is possible to increase the effectiveness of radiation or chemotherapy, and the patients live longer as a result.
Therefore, Carter and the doctors and residents he oversees as chair of the Department of Neurosurgery at the UC San Diego School of Medicine strive to enhance brain cancer treatment by developing some of the methods that Carter delved into while at Mass General.
One of these methods is called liquid biopsy.
“Let’s say a patient comes in with weakness of the hand, or a speech problem, or perhaps he or she has had a seizure. In any of those scenarios, the first thing that an ER doctor or primary care physician does is order an MRI scan. On the MRI scan you usually see a white spot, which indicates a high likelihood that a tumor is present,” Carter said. “But we don’t know when looking at the MRI exactly what type of tumor it is.
Normally, surgeons have to drill a hole in the patient’s head and pass a probe down into the brain to perform a biopsy and determine what kind of tumor the patient has. By contrast, liquid biopsy requires only a sample of the patient’s blood or spinal fluid, which is then analyzed for genetic markers of the tumor. Almost every brain cancer has a genetic-specific marker or sign of a DNA mutation. Doctors who analyze the blood or fluid sample can match the genetic marker to identify the patient’s corresponding brain cancer.
Carter thinks the reason the genetic marker ends up in a person’s blood is that brain tumors release small-membrane-bound packages of information called exosomes, which transport genetic signals from the tumor to the surrounding microenvironment of normal brain tissue. This causes the local brain tissue to change in multiple ways, including hiding the brain tumor from the body’s immune system. The information in the exosomes also signals brain blood vessels to infiltrate the tumor so the tumor receives the necessary blood supply for continued growth. The exosomes are also released into the patient’s blood or spinal fluid. The exosomes have the DNA and RNA markers from the tumor that inform the treating physicians what type of brain tumor the patient has.
Even though a brain tumor may find ways to hide itself from the immune system, Carter has fought back by developing chimeric antigen receptor (CAR) T-cells as a new treatment for brain cancer. Each normal T-cell has a receptor that recognizes a foreign protein. CAR T-cell therapy involves harvesting T-cells from a patient’s blood, exposing the T-cells to a virus or nucleic acid to “teach” the T-cells to attack proteins commonly found in most brain tumors, and then the T-cells are returned back into the patient. One of the proteins they are taught to attack is called EGFRvIII. That protein is found in 30 to 35 percent of patients with brain tumors.
Carter has also improved neurosurgical technique by helping develop what is called florescence-guided brain surgery. In this new concept, a patient consumes a fluorescent-imaging drug an hour and a half before surgery. The drug enters the tumor and causes it to fluoresce when exposed to blue light. This allows doctors to distinguish the cancer cells from the healthy brain tissue and perform a more precise and safe removal of the tumor while avoiding normal cells.
Carter has also worked with BYU students who spend a summer at UC San Diego School of Medicine to get a feel for the medical field.
He has been called back to where it all started, to be the chair of the Department of Neurosurgery at Mass General and Harvard Medical School, starting February 1, 2017, after being at UC San Diego since 2010. Carter said he is looking forward to the challenge of working as the chair at the third oldest hospital in the United States with its high expectations and history of innovation and progress.
“People expect the Mass General to lead out, and so I have to lead the team that can make that happen,” Carter said.