Dr. Daniela Bota was born into a family of successful engineers in Romania. A national mathematics champion in her youth, her family expected her to follow into the dispassionate but intellectually challenging field of engineering. But it was the plight of people, not machines, that called her to a career in medicine.
“Learning how machines work was not what interested me,” says Bota, who directs the UCI Health Comprehensive Brain Tumor Program. “I wanted to bring the understanding of deep scientific processes to medicine. I was always interested in finding out how people get sick and how to help them get better.”
Patients have been the beneficiaries of Bota’s desire to follow her heart. In her years in medicine, the neuro-oncologist has performed research that has pushed the boundaries of innovation in a quest to improve the survival rates of people with brain tumors, including the most aggressive type of brain cancer, glioblastoma.
Bota attended medical school in Bucharest then moved to California where she earned a PhD in molecular biology at the University of Southern California. She also trained as a neurologist and found herself drawn to patients who were fighting brain cancer.
A drive for clinical research
“I became immensely invested — scientifically and emotionally — in patients with brain tumors,” she says. “I find this to be such a rewarding field. They are generous patients who are interested in participating in clinical research and helping us move knowledge to future patients.”
Bota is at the forefront of brain tumor research. She is leading a study on a cancer vaccine that consists of using the patient’s own cells, which are treated and injected into the patient to trigger a cancer-fighting immune response. She also is one of the few U.S. doctors enrolling patients in a Phase 1 study of a promising drug called marizomib to fight glioblastoma. And she’s supervising studies on the effects of chemotherapy on brain function — the malady characterized by mental fogginess that patients often refer to as “chemo brain.”
Clinical trials often offer cancer patients a unique advantage: the chance to try promising therapies before they become widely available. Bota says she’s touched every day by the courage and generosity of her patients who enter trials.
“The patients realize they are at a very important point in their lives. That can bring out the most beautiful characteristics in people. It makes them more altruistic,” she says.
“Even if they don’t have a long life ahead of them, they still give the time that they have to help science. We know we don’t have enough treatments for these diseases. So every patient in a clinical trial helps us and future patients.”
Lengthening brain tumor survival
Increasingly such innovative treatments appear to be working. “There are more and more success stories,” she says. “The treatment of brain tumors used to be a sprint. Now we are looking at it as a marathon. It’s about being able to offer the newest treatments. That’s what we do so well at UCI Health through our programs and clinical trials — we try to prolong the time of tumor remission.”
Advances in radiation therapy, surgery, immunotherapy and other innovative treatments are improving the prognosis for many cancer patients. Bota has been a leader in the use of Optune, a novel device worn on the head that generates an electrical field to disrupt the growth of cancer cells.
The ability to offer such advanced therapies depends on the multidisciplinary collaboration among her colleagues at the UC Irvine Chao Family Comprehensive Cancer Center, especially her fellow neuro-oncologists Dr. Jose Carrillo and Dr. Xiao-Tang Kong.
“We work as a team. We are friends. We are partners. We are collaborators. This is a war, and we’re going to war together. To have that kind of support is amazing.”
The team also includes neuroradiologists and radiation oncologists, who are skilled in the latest neuro-imaging and neuro-radiation technologies, as well as neurosurgeons, who are experts in minimally invasive approaches to tumor removal that reduce the risk of damage to healthy brain tissue. They also are able to extract previously inoperable tumors. These neurosurgeons possess extremely high resection rates, Bota says.
Safely removing tumors
“The extent of resection [removal of the tumor] correlates with patient survival,” she explains.
“But if the patient is paralyzed or unable to speak after resecting the tumor, survival goes down and the patient has symptoms that make for a poor quality of life. The question is how to take out the tumor safely. This is why it’s significant that we have neurosurgeons who are fellowship trained in neurological oncology and who treat a larger number of patients than those at most other institutions.”
UCI Health treats the largest number of brain cancer patients in Orange County and ranks sixth overall in California. The program’s state-of-the-art technology for imaging and mapping the brain accounts for improved success rates, she says.
“We do a great deal of work to prepare for surgery,” she says. “We are able to map the brain by doing functional imaging and fusing images to produce complete maps of the brain. Those maps are transferred to our operating room computers, and our surgeons use these to guide them. Those kinds of preparations before surgery are what allow us to have this excellent rate of resection while preserving neurological function.”
Although as a physician-scientist Bota spends a lot time in her lab working on new treatments, she says seeing patients is a priority.
“The most satisfying thing to me is being able to tell a patient that they are in remission. They may have been told, at other institutions, that they have six months to live. But we can offer them treatments here, such as clinical trials, that could prolong their lives. That’s the most amazing thing. That’s why I come to work every day.”
Cancer vaccines hold promise
Cancer vaccines are emerging as a potential tool to fight glioblastoma, the deadliest type of brain cancer. Even after surgery, chemotherapy and radiation, these cancer cells often remain. Bota says vaccines may prove a successful way to target and destroy those elusive cancer cells.
Bota is leading a clinical trial that involves blending cells from a patient’s tumor cells from other patients with similar cancers in order to stimulate an immune response. When the mixture is injected back into the body, the vaccine reprograms the individual’s immune system to identify and kill the cancer cells.
“Vaccines are part of the future of cancer therapy,” Bota says. “However we still have to figure out what is the best combination of treatments. How can we create vaccines that are more effective, and how can we use them in combination? I don’t think we’ll have one therapy that will cure all patients. The question is how can we combine therapies?”
IV drug therapy
Bota is one of a handful of neuro-oncologists enrolling U.S. patients in a Phase 1 clinical study of the use of an intravenous form of the drug marizomib to treat glioblastoma. Marizomib is a highly potent proteasome inhibitor; the proteasome pathway plays a vital role in the physiology of glioblastoma.
Bota helped develop the therapy in her lab in cooperation with a pharmaceutical company that was exploring the drug for a different type of cancer. “We’re seeing promising results and getting more funding,” she says. “We want to test the drug not just in patients who are failing all other therapies but in newly diagnosed patients.”
Reversing 'chemo brain'
Some people who undergo chemotherapy treatment experience fuzzy thinking and a mental dullness, a condition often called “chemo brain” that has long been recognized in the field of cancer treatment. Although the brain typically recovers after treatment, it lingers in some people for years.
Bota, who has received funding from the National Institutes of Health to study chemo brain, discovered that the commonly used chemotherapy drug cisplatin causes chemo brain symptoms in rats. Studies also showed that a different medication may help reverse these effects. She hopes to launch a human “chemo brain” clinical trial soon.
Electric field therapy
Optune, previously called NovoTTF, is a unique therapy suitable for some patients with glioblastoma. The cap like device generates an electrical field that disrupts the cell division that is a hallmark of cancer. Users regularly wear the cap, which is attached to a small battery pack that powers the system. UCI Health is one of the few institutions on the West Coast to offer the therapy.
Bota says previous studies show that survival for newly-diagnosed glioblastoma patients who were using the device increased, on average, more than four months. Optune also is considered a good option for patients with recurrent glioblastoma.
Initially, the device was approved for patients whose tumors had grown after conventional treatment. But the U.S. Food and Drug Administration recently approved the device for patients whose tumors are stable following surgery, radiation and chemotherapy.
“This approval will allow all of our patients to go on the device if they want to,” Bota says.