Glioblastoma – Health Care
Tag

Glioblastoma

Browsing

When you're facing a cancer diagnosis with an average survival span of 12 to 18 months, every milestone is a victory. That makes each wedding invitation, graduation announcement and birthday photo that UCI neuro-oncologist Dr. Daniela Bota receives from her patients a cherished validation of her 12 years of groundbreaking research on glioblastoma multiforme, the most aggressive form of brain cancer. "Because of our work, these people have been able to move on with their lives," she says.

Bota has pushed the boundaries of innovation in her quest to increase the survival rates of individuals with brain tumors, especially glioblastomas. The esteemed physician-scientist has taken a truly comprehensive approach to battling this rare disease, which has a five year survival rate of only 10 percent and claimed the lives of U.S. Sens. Ted Kennedy and John McCain. Bota has conducted clinical trials of multiple cutting-edge treatments that are improving the quantity as well as the quality of life for glioblastoma patients at UCI and beyond.

'So much potential, so much growth'

Bota grew up in Romania, in a family of engineers. It was assumed she'd follow them into the profession – she was a national mathematics champion in her youth – but Bota had another path in mind. "I wanted to make a more significant contribution," she says. "I wanted to combine my analytical side with a place where I could help others. I ended up becoming an M.D.-Ph.D. to blend both."

At USC, Bota earned a doctorate in molecular biology, focusing on neural degeneration. She then went to the University of Kansas for medical school and a residency in neurology. During her shifts, Bota found herself caring for people with brain tumors – and discovered a new direction for her medical career.

The generosity and gratitude of brain tumor patients make it so rewarding to care for them. I see it again and again at UCI. Many of these patients have a terminal diagnosis, but they're volunteering their time and energy to participate in our clinical trials to help us build a better treatment and, hopefully, in the future, a cure."

Dr. Daniela Bota, UCI neuro-oncologist

After a neuro-oncology fellowship at Duke University, Bota joined the faculty of UCI's School of Medicine and the Chao Family Comprehensive Cancer Center in November 2007. "Both my career and UCI in general have grown so tremendously over the dozen years since," says Bota, who's now co-director of the UCI Health Comprehensive Brain Tumor Program. "There has been so much potential, so much growth, so many changes and so much scientific revolution helping us move forward in so many different directions. It's a very exciting time."

A comprehensive approach

The word "comprehensive" carries significant weight in the realm of cancer care centers. The "comprehensive" designation from the National Cancer Institute recognizes an added depth and breadth of research that bridges multiple scientific areas. Just 51 cancer centers in the U.S. carry the designation; the Chao Family Comprehensive Cancer Center is the only one in Orange County. "We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world," Bota says.

Her own multipronged attack against glioblastoma multiforme reflects the center's comprehensive approach. Bota's work on the experimental drug marizomib has generated significant attention and hope. Unlike traditional chemotherapy drugs, marizomib can penetrate the blood-brain barrier – the filtering mechanism that prevents many blood-borne substances from passing into brain tissues – and inhibit cancer growth without causing damage to other parts of the brain.

Over the past 12 years, Bota has shepherded marizomib from preclinical development all the way through a 700-person international phase III clinical trial now underway. "We have a number of patients from our clinical trials who are surviving this tumor for longer periods of time than usually expected," she says.

Related Stories

  • Finding new clues to combat glioblastoma
  • Cancer risk in psoriatic patients
  • UCLA researcher designs ways for immune cells to 'outsmart' solid tumors

Amanda Johnson, a 32-year-old freelance writer in Mission Viejo, has been receiving marizomib for two years under Bota's care. Her large glioblastoma tumor – which straddled both sides of her brain – has shrunk so much that it's no longer measurable. She has returned to work on her novel and even joined a gym. "I feel so happy just to be alive," Johnson says.

Larry Johnson, her father, told Fox News, "I don't think [Amanda] has come to realize how important her survival is to other people and families who are going to find themselves in a similar situation."

Bota strives to reach a point where such cases will be so commonplace that they don't make the news. "That's what success looks like – not having a prominent publication or being part of a game-changing discovery," she says. "It's having patients like Amanda still be here and doing well."

Vaccine trials and right to try

To achieve that goal, Bota tenaciously pursues multiple avenues of treatment. She has been a leader in the use of Optune, a device worn on the head that generates an electrical field that disrupts the growth of cancer cells. "We were among the first in the country to explore and use this technology," Bota says. "Now we're working with physicians from other countries to help them adopt it in their practices."

She is also spearheading two clinical trials on cancer vaccines. "Brain tumors hide behind the blood-brain barrier, so the body doesn't recognize them as not being a normal part of the body," Bota explains. "With our vaccines, we extract cellular markers from the patient's tumor and inject them back into the patient to stimulate the immune system to recognize those tumors, attack them and, if possible, eliminate them."

She adds: "Both studies have been well-received in our neuro-oncological community, which is highly promising. And a significant benefit is that the vaccines function with minimal or no toxicity."

In January 2019, one of Bota's patients who was ineligible for both clinical trials was able to access one of the vaccines through the first successful application of the national Right to Try Act. Passed in May 2018, it allows people with terminal illnesses, in consultation with their doctors, to seek treatment with experimental drugs not yet approved by the Food and Drug Administration directly from pharmaceutical companies. "The law puts patients in charge of their care; they initiate contact with the manufacturer and request therapy," Bota says. "It gives patients who don't qualify for clinical trials another option."

"We offer one of the most innovative and complex portfolios of clinical trials anywhere in the world."

Sharing her expertise

Bota eagerly offers her knowledge beyond the doors of the Chao Family Comprehensive Cancer Center. Whenever she and her husband, Robert, a local psychiatrist, travel back to their home country of Romania, she consults with medical colleagues there, as there are no certified neuro-oncologists in the nation. On days when the couple work on their farm in the Transylvanian Alps, locals come to them – often on foot – for medical advice. The two hope to eventually establish a clinic in the area. "I want to make sure that Romania also benefits from my medical expertise," Bota says.

Back on campus, in her capacity as senior associate dean for clinical research, she uses her vast clinical trial experience to help colleagues in UCI's School of Medicine advance their own research projects into the clinical arena.

"I'm excited by the ability to impact the lives of so many people through this role," Bota says. "Whether it's for burns or vascular disorders or other conditions, people come to UCI for the same reason: We can offer what community hospitals cannot. Being able to make that happen, to create new options for our patients, is what wakes me up in the morning."

Source:

University of California, Irvine

A new simple blood test for brain tumors that could be used by GPs in primary care is being developed thanks to funding of nearly £500,000 by Cancer Research UK. Around 60,000 patients in the UK are living with a brain tumor but only 20 per cent of patients are still alive five years after diagnosis, partly because they present late with large inoperable tumors.

The University of Bristol-led research project to develop an affordable, point of care blood test to diagnose brain tumors earlier using fluorescent carbon dots and nanophotonics will be headed by Dr. Kathreena Kurian, Associate Professor in Brain Tumour Research and Dr. Sabine Hauert, Senior Lecturer in Robotics in collaboration with co-investigators: Professors Carmen Galan and Richard Martin at the University of Bristol; Dr. Neciah Dorh at FluoretiQ Limited and Dr. Helen Bulbeck at Brainstrust.

The cross-disciplinary research project brings together medical practitioners, along with experts in population health, nanoparticle engineering and detection, as well as computational modeling.

Dr. Kathreena Kurian, Head of the Brain Tumour Research Centre at the University of Bristol, said:

A simple blood test carried out by GPs would help decision-making and early diagnosis. This would revolutionize care by speeding up diagnosis, reducing costs to the NHS, anxiety of unnecessary scans and reducing the number of patients presenting with inoperable large brain tumors.

Additionally, this test could be used as an early monitor of brain tumor recurrence. Our work will be followed by a multicentre cohort biomarker study to determine the effectiveness of the test in a real-world setting."

Dr. Sabine Hauert from the Department of Engineering Mathematics and Bristol Robotics Laboratory (BRL), added: "Nanoparticles have shown promise in early detection of cancer by fluorescent labeling of very low levels of biomarkers in blood samples and other fluids."

Dr. Alexis Webb, Cancer Research UK's senior early detection funding manager, said:

At the moment the number of people who survive after a brain tumor diagnosis remains low and little has changed in over a generation. We're proud to support this innovative project and funding brain tumor research remains a priority for the charity. We need better techniques to diagnose brain tumors earlier, when more treatment options are available, to secure a future for more people affected by the disease."

Professor Carmen Galan, Professor of Organic and Biological Chemistry in the School of Chemistry, who has developed the fluorescent carbon-based nanomaterials that form the basis for the project, explained: "The fluorescent nanoprobes are produced by low-cost renewable routes and we have shown that we can decorate them with different biomolecules to target specific biomarkers in physiological conditions, which is really exciting."

Dr. Neciah Dorh, CEO of FluoretiQ Limited, stated:

As a diagnostics company, we are passionate about creating technology that can improve people's lives and we see this project as natural extension of the work that we are currently doing in infectious disease."

Related Stories

  • Researchers design new drug cocktail to kill brain and soft tissue cancers
  • New drug offers hope for preserving brain cells for a time after stroke
  • Brain activity can reveal empathy

In the UK in 2013, 38 percent of brain tumor patients visited their GP five times or more before being referred for diagnosis by imaging MRI/CT scan and neurosurgical biopsy, because the symptoms such as headache are non-specific, so there is an urgent need to develop new tests for brain tumors to help GPs diagnose brain tumors earlier.

There is a pressing need for the discovery of new blood biomarkers for brain cancer and state-of-the-art technology that allows for its sensitive detection. The aims of the research project are:

  • discover novel biomarkers, in addition to known markers such as Glial fibrillary acidic protein (GFAP), which will be used as a baseline;
  • implement a computational model to predict biomarker levels in blood;
  • develop a fluorescent nanoparticle that can label this marker in blood;
  • work with Bristol-based start-up FluoretiQ towards an affordable near patient testing solution.

Glioblastoma is the most common type of malignant brain tumor among adults and it is usually very aggressive, which means it can grow fast and spread quickly. It is characterized by abnormal blood vessels following a leaky blood-brain barrier (BBB). GFAP is unique to the brain and not present in blood that circulates throughout the body. Antibodies in GFAP are used to diagnose gliomas in tissue samples. There is evidence that GFAP crosses the leaky BBB and is an early non-specific peripheral blood biomarker which predates the clinical diagnosis of glioblastoma.

However, GFAP levels are too low for routine detection by routine protein detection tests such as ELISA. The research team has already identified other novel potential protein biomarkers of brain tumours using the epidemiological method, Mendelian Randomization, which may be present in low levels in the blood.

Fluorescent carbon dots (FCDs), also known as nanoparticles, are cheap and easy to create using a three-minute synthesis. FCDs can be readily attached to ligands such as antibodies targeting specific protein markers. FCDs labeling biomarkers can then be detected using nanophotonic technology, which has been developed by FluoretiQ, for rapid, sensitive, and low-cost diagnosis. Computational modeling will then be used to predict tumor size given biomarker availability in blood and establish the theoretical limits of the detection.

Source:

University of Bristol