Working on Two Fronts

As a researcher and physician, Dr. Daniela Bota cares for patients while trying to find cures.

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 Bota to a career in medicine.

“Learning how machines work was not what interested me,” she says. “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 this brilliant woman’s desire to follow her heart. In her nine years in medicine, all spent at UC Irvine Health, the neuro-oncologist has performed research and pushed the boundaries of innovation in a quest to improve the survival rates of people with brain tumors, including the dangerous brain cancer known as glioblastoma.

Bota attended medical school in Bucharest and then moved to California to earn a doctoral degree in molecular biology at the University of Southern California. She trained as a neurologist but was drawn to patients who were fighting brain cancer.

“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. And Bota is one of the few U.S. doctors enrolling patients in a Phase 1 study of a promising drug called marizomib to fight glioblastoma. She’s also supervising studies on the effects of chemotherapy on brain function—the malady characterized by mental fogginess that patients often refer to as “chemo brain.”

“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.”

Clinical trials often offer cancer patients a unique advantage: the chance to try promising therapies before they become widely available. But Bota says she’s touched every day by the courage and generosity of her patients.

“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.”

But increasingly such innovative treatments are 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 UC Irvine 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 have also improved 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 UC Irvine Health professionals, she says of her colleagues at the Chao Family Comprehensive Cancer Center. “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.”

She praises two colleagues, both board-certified in neuro-oncology, who step in and shoulder some of her clinical duties when Bota must devote time to research, travel to international medical meetings or grant writing to raise funds for research. But she never stays away from her patients for long.

“I’m a physician-scientist; I spend a lot of time in the lab trying to bring new treatments to patients,” she says. “But 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.”

Innovations in Brain Cancer Treatment

Cancer vaccines are emerging as a potential tool to fight glioblastoma, the deadliest type of brain cancer. Even after surgery, chemotherapy and radiation, cancer cells often remain. Vaccines may prove to be a successful way to target and destroy those remaining, elusive cancer cells.

UC Irvine Health offers several vaccine trials. Most of these vaccines are designed to prompt the patient’s immune system to destroy remaining cancer cells. Dr. Daniela Bota is leading a clinical trial in which cells from a patient’s tumor are blended in a laboratory with tumors from other patients with similar cancers, with the purpose of stimulating the immune response. When injected back into the body, this vaccine programs the individual’s immune system to identify and kill cancer cells.

“I think 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?”

Dr. Daniela Bota is currently one of only three doctors in the United States enrolling patients in a Phase 1 clinical study to use 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. A Phase 1–2 trial is underway at UC Irvine Health.

“This is an amazing story,” she says. “We’re seeing promising results and getting more funding. We want to test the drug in not just patients who are failing all other therapies but in newly diagnosed patients.”

Chemo brain is a condition long recognized in the field of cancer treatment. Some people who are undergoing chemotherapy treatment experience fuzzy thinking and a mental dullness. Although the brain typically recovers following treatment, some people have the condition for years.

Research on the condition has been scarce until recently. Dr. Daniela Bota has received funding from the National Institutes of Health to study chemo brain and recently found that cisplatin, a commonly used chemotherapy drug, causes the symptoms in rats. Studies also showed that a different medication may help reverse the effects. The data have been submitted for publication, and Bota hopes to launch a human clinical trial soon.

“We are very, very excited about this work,” she says. “We are finding new mechanisms through which chemotherapy affects the brain and creates memory problems.”

Optune, previously called NovoTTF, is a unique therapy suitable for some patients with the brain cancer glioblastoma. The device is a caplike device that the patient wears on a regular basis. The cap generates an electrical field that disrupts the cell division that is a hallmark of cancer. Users carry a small battery pack that powers the system. UC Irvine Medical Center has been one of the few institutions on the West Coast to offer the therapy.

Previous studies show that survival for newly-diagnosed glioblastoma patients using the device increased, on average, more than four months. Optune is a good option also for recurrent glioblastoma patients.

Previously the device was approved for patients whose tumors had grown after conventional treatment. But recently the Food and Drug Administration 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,” says Dr. Daniela Bota.

For challenging tumors such as glioblastoma, multiple therapies are needed, such as surgery, radiation, chemotherapy and other novel treatments. All members of these specialty areas, including nurses, social workers, nutritionists and others, are called upon to support patients. “We are specially and uniquely able to do that at UC Irvine Health,” says Dr. Daniela Bota.

The Chao Family Comprehensive Cancer Center is home to a full complement of the latest neuro-imaging and neuro-radiation technologies, she says. Moreover, UC Irvine Health neurosurgeons are skilled in minimally invasive approaches to surgery that reduce the risk of damage to healthy brain tissue. These surgeons possess extremely high resection rates, Bota says.

“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 which are fellowship trained in neurological oncology and who treat a larger number of patients than most institutions.”

UC Irvine Health treats the largest number of brain cancer patients in Orange County and ranks sixth overall in California. The state-of-the-art technology to image and map the brain allows for high success rates, she says.

“We do a great amount of work in preparation for the surgery,” she says. “We have a very good neuro-radiology program where we are able to map the brain by doing functional imaging and fusing brain images to produce complete maps of the brain. Those maps are transferred to our operating room computers, and our surgeons use that to guide them. Those kinds of preparations before surgery are what allows us to have this excellent rate of resection while preserving neurological function.”