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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.

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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

Earlier this year, doctors and researchers celebrated the news that the five-year survival rate for pancreatic cancer had crossed into double digits for the first time -; up from just 6% in 2011.

And while researchers at the University of Michigan Rogel Cancer Center and elsewhere continue to pursue scientific insights into the disease and develop new therapeutic approaches, surgeons on the front line of patient care are also working hard to improve outcomes.

Hari Nathan, M.D., Ph.D., an assistant professor of surgery at Michigan Medicine, sat down with the Michigan Health blog to talk about recent advances in surgical care for patients with pancreatic cancer, and some things patients should look for when evaluating where to seek treatment.

Growing evidence that starting chemo before surgery could improve survival

The best approach for treating pancreatic cancer remains physically removing the cancer through surgery, also called resection, in combination with chemotherapy and sometimes radiation therapy, Nathan says.

"It's been known for decades that adding chemotherapy to resection for pancreas cancer improves survival," he says. "It's a very difficult disease to begin with, and the survival rates are still unacceptably low compared to the progress we have made in a variety of other cancers. But rates are improving -; and part of the reason they're improving is the development of more effective chemotherapy regimens over time."

Recently, surgeons at Michigan Medicine have adopted an emerging practice of administering some or all of a patient's chemotherapy before they undergo an operation.

One recent study, for example, found that patients who underwent chemo before surgery -; known as neoadjuvant chemotherapy -; had a two-year survival rate of 63.7% compared to 53.5% in those who received surgery first.

That difference is driven by multiple reasons. Even in the best hands, these operations are challenging and can be fraught with complications. And we know that when we give chemotherapy after an operation, roughly half of patients aren't healthy enough to complete the intended course."

Hari Nathan, M.D., Ph.D., assistant professor of surgery at Michigan Medicine

Giving chemotherapy on the front end -; before a major operation takes a toll on a patient's body -; increases the likelihood they'll complete more of their chemotherapy, which, in turn, is correlated with better outcomes, he notes.

For some patients, earlier administration of chemotherapy could spare them from going through an operation if there are signs it won't be effective.

"A small percentage of patients will develop additional disease during chemotherapy, or have progression of the tumor," Nathan says. "That's a warning sign that their disease is more aggressive and putting them through a major operation may not be helpful to them."

Helping more patients become candidates for surgery

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In addition to improving the number of patients who complete their course of chemo, the neoadjuvant approach is also expanding the number of patients who are candidates for surgery, Nathan says.

"What we often find with these newer chemotherapy regimens is that they actually can kill parts of the tumor that will make an operation more viable," he says.

In the past, a patient may have been told that their tumor wasn't resectable because it was wrapped around a vital artery.

"But if we can kill off the part of the tumor that was a barrier to a successful surgery, then it makes it possible to go in and do the operation," Nathan says.

"In a lot of ways, what we're doing in pancreatic cancer now mimics what we've been doing in other cancers for a while," he adds. "The difference is that in colorectal cancer, for example, we've had more effective chemotherapy agents, and so we've been willing to be more surgically aggressive. And now with pancreatic cancer, we're finally getting to that point where we have these more effective chemotherapy regimens."

Where patients get care can make a big difference

There are a number of reasons why receiving care at a nationally ranked hospital or academic medical center, like Michigan Medicine, can also make a big difference for patients, Nathan says.

The first is access to new, otherwise unavailable experimental treatments through clinical trials.

For example, Nathan says, U-M is a site for a trial enrolling patients who are not initially eligible for surgery because their pancreatic cancer involves major blood vessels or other tissue in the abdomen. The trial is to test an investigational medicine that helps chemotherapy to better attack the tumor, with a goal, ultimately, of making the patients candidates for surgery.

Second, larger, high-volume, multidisciplinary centers will have more experience in specifically treating pancreatic cancer (Michigan Medicine was recently designated a National Pancreas Foundation Center of Excellence for Pancreatic Cancer, one of just two in the state.)

"I would argue that medical centers like U-M, by virtue of the breadth and depth of the system as a whole, can provide the highest quality care," Nathan says. "In addition to the quality of our surgeons, our medical oncologists, radiation oncologists, radiologists, geneticists and nutritionists all have expertise in pancreatic cancer. Everybody in our multidisciplinary pancreatic clinic has a large focus of their practice devoted to taking care of patients with pancreas cancer. That's not the case everywhere."

Source:

Michigan Medicine – University of Michigan

The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded new grants totaling $1.8 million to two University of Texas at Dallas scientists for their research related to lung and kidney cancers.

The Individual Investigator Awards are among 55 new grants totaling more than $78 million that the institute announced Feb. 19. To date, CPRIT has awarded $2.49 billion in grants to Texas research institutions and organizations through its academic research, prevention and product development research programs.

With the latest grants to the researchers in the School of Natural Sciences and Mathematics, UT Dallas has received nearly $18.5 million from CPRIT to support cancer studies.

CPRIT continues to be an important source of funding for efforts aimed at the prevention and treatment of cancer. The institute's ongoing support of basic research allows UT Dallas scientists to make important contributions toward the fundamental understanding of disease and the improvement of outcomes for cancer patients."

Dr. Joseph Pancrazio, vice president for research and professor of bioengineering at UT Dallas

Dr. Li Zhang, professor of biological sciences and the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science, received $900,000 for lung cancer research. In previous studies, Zhang and her colleagues discovered that cells of the most common type of lung cancer — non-small cell lung cancer — consume substantially more oxygen than normal cells. The lung cancer cells also outpace their normal counterparts in synthesizing a critical chemical called heme, which helps transport and store oxygen. These elevated levels of oxygen and heme fuel tumor growth and progression.

With the new CPRIT grant, Zhang will use advanced imaging techniques in animal models to investigate whether drugs that target heme synthesis and uptake can be a successful strategy for suppressing lung tumors and improving the effectiveness of chemotherapy, radiotherapy and immunotherapy.

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Zhang previously received a CPRIT grant of $900,000 in 2015.

Dr. Jie Zheng, professor of chemistry and biochemistry and the Cecil H. and Ida Green Professor in Systems Biology Science, also received $900,000 for his research, which is aimed at improving the accuracy of computerized tomography (CT)- and fluorescence-guided kidney cancer surgery.

With more kidney cancers being diagnosed in the early stage, partial kidney removal is becoming an increasingly important treatment, in particular for those patients who have poor kidney function or cancer in both kidneys. In current clinical settings, CT is used first to noninvasively localize and stage kidney cancers, followed by fluorescence imaging of normal renal tissue to guide surgery. However, due to the limitations of current contrast agents, no significant improvement in reducing positive margin rates in kidney cancer surgery has been achieved, Zheng said.

Zheng's project will focus on developing a single material, based on gold nanoparticles, that can achieve high contrast in both CT and fluorescence imaging of kidney cancers. His approach takes advantage of the unique physiological microenvironment associated with kidney cancer in a way that allows the tumor margins to be more accurately differentiated during surgical removal. His nanoparticles also have the potential to effectively and selectively deliver anti-cancer drugs to tumors that cannot be treated surgically.

Zheng received three previous CPRIT grants in 2011, 2014 and 2016 totaling nearly $2.4 million.

Source:

University of Texas at Dallas

Modern anticancer therapies aim to attack tumor cells while sparing healthy tissue. An interdisciplinary team of researchers at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and FU Berlin has made important progress in this area: the scientists have produced tiny nanoparticles that are designed to specifically target cancer cells. They can navigate directly to the tumor cells and visualize those using advanced imaging techniques. Both in petri dishes and animal models, the scientists were able to effectively guide the nanoparticles to the cancer cells. The next step is to combine the new technique with therapeutic approaches.

The HZDR researchers start out with tiny, biocompatible nanoparticles made of so-called dendritic polyglycerols that serve as carrier molecules.

We can modify these particles and introduce various functions. For example, we can attach an antibody fragment to the particle that specifically binds to cancer cells. This antibody fragment is our targeting moiety that directs the nanoparticle to the tumor."

Dr. Kristof Zarschler, research associate at HZDR's Institute of Radiopharmaceutical Cancer Research

The target of the modified nanoparticles is an antigen known as EGFR (epidermal growth factor receptor). In certain types of cancer, such as breast cancer or head and neck tumors, this protein is overexpressed on the surface of the cells. "We were able to show that our designed nanoparticles preferentially interact with the cancer cells via these receptors," confirms Dr. Holger Stephan, leader of the Nanoscalic Systems Group at HZDR. "In control tests with similar nanoparticles that had been modified with an unspecific antibody, significantly fewer nanoparticles accumulated at the tumor cells."

The scientists intensively studied the nanoparticles' behavior both in cell cultures and in an animal model. For this purpose, they provided the nanoparticles with additional reporter characteristics, as Kristof Zarschler explains: "We used two complementary possibilities. In addition to the antibodies, we attached dye molecules and radionuclides to the nanoparticles. The dye molecule emits in the near infrared spectrum that penetrates the tissue and can be visualized with an appropriate microscope. The dye thus reveals where exactly the nanoparticles are located." The radionuclide, copper-64, fulfils a similar purpose. It emits radiation that is detected by a PET scanner (positron emission tomography). The signals can then be converted into a three-dimensional image that visualizes the distribution of the nanoparticles in the organism.

Excellent properties in living organisms

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Using these imaging techniques, researchers have been able to show that nanoparticle accumulation in the tumor tissue reaches maximum two days after administration to mice. The labelled nanoparticles are subsequently eliminated via the kidneys without being a burden for the body. "They are apparently ideal in size and properties," says Holger Stephan. "Smaller particles are filtered out of the blood in just a few hours and thus only have a short-term impact. If, on the other hand, the particles are too big, they accumulate in the spleen, liver or lungs and cannot be removed from the body via the kidneys and bladder." The interplay between the nanoparticles with an exact size of three nanometers and the attached antibody fragments evidently has a positive influence on the distribution and retention of the antibody in the organism as well as on its excretion profile.

In future experiments, the HZDR researchers want to test whether they can modify their system to carry other components. Kristof Zarschler describes the plans: "You can take these nanoparticles and functionalize them with an active substance. Then you can deliver a drug directly to the tumor. This might be a therapeutic radionuclide that destroys the tumor cells." It is also possible to attach antibody fragments specific for proteins other than EGFR to target different types of cancer.

Source:

Helmholtz-Zentrum Dresden-Rossendorf

Journal reference:

Pant, K., et al. (2019) Active targeting of dendritic polyglycerols for diagnostic cancer imaging. Small. doi.org/10.1002/smll.201905013.