Like most people, John Gifford wasn't looking forward to a colonoscopy when he arrived on the UCI Medical Center campus in Orange in 2018. The Riverside man, 65, was concerned about his family history of colorectal cancer and had dutifully scheduled an appointment with UCI Health gastroenterologist Dr. William Karnes.
The exam turned out to be intriguing and enlightening – a far cry from what one expects during a colonoscopy, Gifford recalls with a laugh. While the day-before prep had been the same annoying process, the test itself featured new technology – pioneered by Karnes, associate clinical professor in UCI's School of Medicine – that uses artificial intelligence to make screening easier and more accurate.
Running the AI program in real time during the exam, Karnes discovered two small precancerous polyps that might have been missed without the technology. He removed them, reducing the risk that his patient will develop colorectal cancer anytime soon.
"It's terrific to find these polyps so early," Gifford says. "AI enhances your comfort level, and it helps reassure you that you're getting the best care possible."
The colonoscopy even seemed easier than the one he had undergone 10 years earlier, he says. "It was pretty much painless," says Gifford, who opted not to receive any anesthesia or moderate sedation and chatted with Karnes as both watched the computer screen. "Normally, you wake up and get a report that's written for your doctor. But when you're going through this, you're seeing the same thing the doctor is seeing. That enhanced the experience for me."
Removing some of the mystery associated with the development of cancer – its randomness and complexity – is foremost on the minds of doctors and researchers on the UCI campus and at the Chao Family Comprehensive Cancer Center in Orange. It's one of only 51 National Cancer Institute-designated comprehensive cancer centers in the nation. That means patients can expect to receive the most advanced cancer care bolstered by a commitment to novel research – such as Karnes' pursuit of AI colonoscopy – says Dr. Susan O'Brien, associate director for clinical science at the Chao Center and medical director of the Sue & Ralph Stern Center for Cancer Clinical Trials & Research.
"What we have here is a continuum from basic science research to being able to translate those discoveries in the lab to clinical trials," she says. "That's the benefit academic medical centers have that other hospitals don't."
At a glance: UCI Chao Family Comprehensive Cancer Center
- Brings together clinicians and researchers from more than 32 departments across six schools at UCI
- Is one of 51 National Cancer Institute-designated comprehensive cancer centers in the country
- Has treatment specialties and subspecialties in 23 types of cancer
- At any given time, offers more than 150 clinical trials testing new cancer treatments, many of them developed by Chao Family Comprehensive Cancer Center members
What is an NCI-designated comprehensive cancer center?
The 51 NCI-designated comprehensive cancer centers in the U.S. must:
- Meet rigorous standards for transdisciplinary, state-of-the-art research focused on developing new
- and better approaches to preventing, diagnosing and treating cancer
- Demonstrate excellence in laboratory, clinical and population-based research
- Train and educate biomedical researchers and healthcare professionals
- Take steps to alleviate the specific burden of cancer on the population served by the center
Stopping cancer before it starts
The NCI designation also means that doctors are focused not only on treating and curing cancer but on cancer prevention and early detection, notes Dr. Richard Van Etten, director of the Chao Center and a professor of medicine in the Division of Hematology/Oncology.
"Most cancers are diagnosed too late," he says. "For a lot of cancers, the major route to a cure is surgery, and that will only work if you catch them early. Among the things that will transform oncology in the future are ways to detect cancer early."
"Cancer is not one disease; it's about 150 different diseases – and we have national experts in all of them. That allows our doctors to be the most up to date on the latest treatments and clinical trials. Many cancer patients will ultimately relapse after initial treatment and will no longer have standard treatment options. That's where we come in with our clinical trials," says Dr. Richard Van Etten, director of the Chao Family Comprehensive Cancer Center.
UCI has made tremendous strides in the prevention and early detection of gastrointestinal cancers, says Dr. Kenneth Chang, executive director of the H.H. Chao Comprehensive Digestive Disease Center in Orange. The center has the only endowed chair in the country devoted to treating cancer with endoscopy – a minimally invasive procedure that spares patients open surgery.
"We know that cancer has a timeline," says Chang, who holds the Vincent and Anna Kong Chair in Gastrointestinal Endoscopic Oncology. "The very first cancer cell that appears in the patient's body is the earliest stage. Then it continues to grow and metastasize until it gets to an advanced stage. But almost all cancers have a precancerous stage when the cells are not normal."
He continues: "There is also what I call a pre-precancer state in which the patient is genetically and environmentally set up for cancer or is at high risk for getting on the cancer spectrum. We're doing a lot of work on early detection, getting rid of precancers and addressing pre-precancers."
For example, Chang says, one strategy begins with acknowledging that obesity is a major risk factor for many forms of cancer, especially digestive tract cancers.
"We're tackling obesity as a pre-precancer," he says. "There are a lot of studies looking at how obesity will overtake smoking as the most detrimental risk factor in cancer incidence and cancer deaths. In practically all of the digestive cancers, obesity is a risk factor."
To address that, UCI has founded a comprehensive, state-of-the-art weight control center offering nutritional counseling, psychological and behavioral programs, integrative health services, weight loss medications, and endoscopic and laparoscopic procedures.
"This is about moving from disease to health," Chang says. "This is the future of medicine. We can genetically profile people, alter their environments and risk factors, and do proper cancer screening."
Advances in screening are leading to better detection of precancerous lesions. UCI has been at the forefront of efforts to identify precancers that can develop into stomach, pancreatic, esophageal and colon cancer, as illustrated by Karnes' AI colonoscopy program. "The work of Dr. Karnes with AI is super exciting," Chang says. "It's a game-changer."
UCI researchers also are pioneering imaging technologies, such as optical coherence tomography, that utilize an endoscopic device to map the esophagus and examine individual cell clusters that indicate Barrett's esophagus, a condition that can evolve into esophageal cancer.
"We've got an amazing technical ability to detect and stage esophageal precancers as well as get rid of them," Chang says. "That's huge, because if you stop Barrett's, your risk of cancer goes back to that of your neighbor."
Barrett's esophagus can be treated in several ways, including radiofrequency ablation – a procedure that Chang helped develop in which an electrical conduction system heats and destroys abnormal cells.
"UCI has become a breeding ground of innovation," he says.
Matching treatments to patients
On the opposite end of the cancer spectrum, UCI's clinicians have access to the latest methods to cure many cancer patients, especially those with early-stage disease, and extend the lives of people with the most challenging and advanced cancers, O'Brien says.
In the last decade, cancer treatment has been transformed by immunotherapy – designed to prod the immune system to fight cancer – as well as targeted therapies, which address the molecular and genetic underpinnings of the disease.
What we have here is a continuum from basic science research to being able to translate those discoveries in the lab to clinical trials. That's the benefit academic medical centers have that other hospitals don't."
Dr. Susan O'Brien
"Historically, our treatment for cancer was basically chemotherapy," O'Brien says. "Chemotherapy can still be quite effective, but it's not very specific, which is why you often have a broad array of side effects. Nowadays, we have more targeted therapies. The side effects are much more tolerable than with chemo. With targeted therapies, we've developed personalized care for patients, so not everyone gets treated the same way."
UCI's doctors make use of targeted therapies and immunotherapy whenever possible while continuing to look for ways to enhance those methods as well as the traditional cancer treatments of surgery, chemotherapy and radiation.
A discovery by Krishnansu S. Tewari, a UCI gynecological oncologist, for example, showed that the drug Avastin could be combined with chemotherapy to extend the lives of women with advanced cervical cancer. His findings were published in February 2014 in The New England Journal of Medicine.
"That led to Food and Drug Administration approval of Avastin for advanced cervical cancer and changed practice in the United States and around the world," Van Etten says.
Rita S. Mehta, a UCI oncologist/hematologist also changed cancer practice globally when she directed a team of researchers who demonstrated that pairing the drugs Faslodex and Arimidex improves survival in women with advanced hormone receptor-positive breast cancer. Her study was published in The New England Journal of Medicine in March 2019.
In addition, Mehta was one of the first physicians in the world to use chemotherapy combined with the drug Herceptin on women with breast cancer before – rather than after – surgery.
The work by Tewari and Mehta underscores the innovation practiced at UCI on a daily basis, Van Etten says. Recent studies show that cancer patients who seek care or consultations at academic medical centers tend to have better outcomes. Area residents with the most complex cancer cases should be referred to UCI for a consultation or second opinion, he adds.
"Cancer is not one disease; it's about 150 different diseases – and we have national experts in all of them," Van Etten says. "That allows our doctors to be the most up to date on the latest treatments and clinical trials. Many cancer patients will ultimately relapse after initial treatment and will no longer have standard treatment options. That's where we come in with our clinical trials."
Fixing a deadly gene mutation
UCI's Chao Family Comprehensive Cancer Center is one of three sites worldwide participating in the first human study of a drug called MRTX849 that could have a revolutionary impact. The drug targets a gene mutation found in 22 percent of all cancers, including half of all colon cancers and one-quarter of lung adenocarcinomas. The KRAS mutation affects how cancer cells grow and divide.
The study, led at UCI by oncologist Sai-Hong Ignatius Ou, a clinical professor in UCI's School of Medicine, will explore the drug's safety and whether it can block the mutation's effects. Study participants are people with KRAS gene mutations who have an advanced cancer that has progressed despite conventional treatment.
"If the drug works, it's going to be almost like a miracle," says Viola W. Zhu, a UCI Health oncologist who works closely with Ou on targeted-therapy trials. "We know this mutation, KRAS, but until now it has not shown itself to be targetable."
Joining forces in research
UCI is home to more than 150 cancer clinical trials at any one time, O'Brien says. Some of them are part of large national or international studies. Others are unique to UCI or have emerged from basic research in campus labs.
Recently, a nationwide clinical trial led by UCI was launched in which doctors will explore whether the nonsteroidal anti-inflammatory drug sulindac and the drug eflornithine, used to treat a parasitic disease called African trypanosomiasis, can prevent recurrence of colon cancer or adenomas, lesions that can develop into cancer. The idea was first proposed by Dr. Jason Zell, a UCI associate professor of hematology/oncology, and Dr. Frank Meyskens, director emeritus of the Chao Center, who shepherded the work from early lab studies to overseeing the trial, dubbed PACES.
"Many clinical trials are on very cutting-edge technologies where the only way a patient would have access to the treatment is to participate in the trial," O'Brien says. "One of the big advantages of participating in a clinical trial is that if an agent turns out to be effective, which many of them do, patients get access well before – sometimes years before – that drug is commercially available."
Improvements in cancer cure rates also will depend on contributions from experts in computational science, mathematics and bioengineering, she notes. With an emphasis on multidisciplinary research, UCI is fertile ground for collaborations that will advance the field, says Tim Downing, an assistant professor of biomedical engineering as well as microbiology & molecular genetics.
"These days, it's less common that going into the lab, closing the door and working by yourself will be fruitful when it comes to understanding and treating highly complex diseases like cancer," he says. "Being at a place like UCI, where the faculty are very collegial and really good at working together, greatly increases the potential for finding real clinical solutions."
On the Irvine campus, Downing's lab is flush with cash after the young professor earned the 2019 Director's New Innovator Award from the National Institutes of Health – one of three early-career UCI researchers to garner the prize last year. The $2.3 million grant will help fund Downing as he uses the tools of mechanobiology to search for new therapeutic approaches to colon cancer and other solid tumors.
Mechanobiology focuses on how physical alterations to cells and the substances that support them – such as collagen and other proteins – can lead to alterations in cellular and genetic functions and, ultimately, to disease. Downing employs next-generation genetic sequencing to explore those cellular differences.
"There hasn't been a lot of work looking at how mechanical processes within solid tumors influence properties of cancer stem cells, which likely play a big role in fueling cancer aggressiveness," he says. "We're proposing to build molecular tools that can be delivered inside cancer cells to correct epigenetic modifications that we know are driving the disease."
Pushing the pace of immunotherapy
Immunotherapy, which spurs the body's immune system to recognize and fight cancer, has revolutionized some cancer treatments in recent years and has the potential to help many more patients. Now a UCI researcher is creating a lab-on-a-chip device to speed up the development of immunotherapy medications.
In the human immune system, T-cells have molecules on their surface that bind to antigens on the surface of foreign or cancer cells. To treat a tumor with T-cell therapy, researchers must first identify exactly which receptor molecules work against a specific tumor's antigens.
UCI's Weian Zhao, associate professor of pharmaceutical sciences, and his colleagues at Caltech, including Nobel laureate David Baltimore, have accelerated that identification process with a prototype technology called droplet microfluidics screening. The device, which is being created by UCI startup Amberstone Biosciences, identifies T-cell receptors for individual tumors within days. Conventional identification techniques can take months or years – time cancer patients often don't have.
Shaping future oncologists
Physicians at academic medical centers are required to stay current with the rapid developments in cancer care for the sake of both their patients and students learning the craft. The UCI School of Medicine places a premium on creating "lifelong learners," says its dean, Dr. Michael J. Stamos.
"What you learn now will be passé in 10 to 20 years," he says. "It's a matter of active learning. That has much more staying power than lecture-style learning."
Reducing the side effects of radiation
Dr. Charles Limoli, a professor of radiation oncology in UCI's School of Medicine, is looking for ways to reduce the cognitive side effects of radiation treatment for brain cancer. Patients who undergo chemotherapy and radiation often complain of mental fatigue and fogginess, commonly referred to as "chemobrain." Limoli has spent his career trying to preserve brain health during cancer treatment.
He's currently analyzing a quick-burst technique called "flash" radiotherapy in which a high dose of radiation is administered in a millisecond – delivering the traditional dose but faster. So far, studies in mice have shown that it reduces side effects related to learning, memory and mood. Limoli and his colleagues are the first to demonstrate that "the flash effect" can diminish long-term cognitive consequences.
"Although more research needs to be done," he says, "this has the potential to revolutionize cancer care worldwide."
Moreover, medical students, fellows, residents and interns benefit from exposure to laboratory research and clinical trials, Stamos says.
"When students see us doing clinical trials, they see that things evolve very rapidly," he says. "That has an undeniable impact."
But the doctors and cancer researchers of tomorrow also learn to see their patients as complex people whose health depends on lifestyle, psychosocial and environmental factors, Stamos says. In 2017, a $200 million gift from Orange County philanthropists Susan and Henry Samueli created a new template for applying science-based approaches to integrative medicine research, education and patient services. The gift will fund the construction of the Susan and Henry Samueli College of Health Sciences on the UCI campus, establish 15 Samueli research chairs across integrative medicine, and support undergraduate and graduate students who plan careers in the field.
"Most cancers are diagnosed too late. For a lot of cancers, the major route to a cure is surgery, and that will only work if you catch them early. Among the things that will transform oncology in the future are ways to detect cancer early."
UCI is fast emerging as a national leader in integrative medicine, which appeals to many cancer patients, Stamos notes. A new mission-based UCI program called HEAL-IM gives medical students the opportunity to learn more about integrative medicine, with an IM focus woven into the entire curriculum. Stamos planned for 18 students in the first class. When 50 applied, he expanded the class to 24 students.
"They clearly have an interest in and are attracted to UCI because of our focus on integrative medicine," he says.
Those doctors are likely to be in high demand. As the huge baby-boom generation ages, cancer incidence rates are projected to rise. UCI intends to be ready for that shift, Van Etten says.
"Cancer is going to overtake heart disease as the No. 1 cause of death in the U.S.," he explains. "Our education and training mission is one of the most important things we do. We're training the next generation of doctors. They will go out in the community and, I hope, become doctors who are on the leading edge of cancer treatment."
Targeting liver cancer
UCI is undertaking research on one of the most novel and personalized approaches to immunotherapy, called chimeric antigen receptor T-cell therapy. It involves taking a patient's own immune cells from blood, re-engineering them, then infusing them back into the patient to prompt his or her immune system to attack cancer cells. Two CAR-T therapies have already been approved by the Food and Drug Administration for blood cancers.
So far, there are no approved CAR-T therapies for patients with solid tumors – such as cancers of the liver, pancreas, lung, colon or ovary.
However, a similar type of immunotherapy research is underway at UCI in which a patient's T-cells are modified to fight advanced hepatocellular carcinoma, an aggressive type of liver cancer. This clinical trial emphasizes UCI's commitment to meeting the specific needs of the region's residents, as required of a comprehensive cancer center, says Dr. Susan O'Brien, associate director for clinical science at the Chao Family Comprehensive Cancer Center and medical director of the Sue & Ralph Stern Center for Cancer Clinical Trials & Research at UCI.
"Hepatocellular cancer is highly prevalent in Asians, and we have a very big Asian population in Orange County," she says. "One of the problems with this cancer is that it's often not detected until it's very far along."
Building a new hospital in Irvine
Residents of Irvine and communities to the south may soon have the added convenience of receiving top-flight cancer treatment, and other medical care, in Irvine.
The planned UCI Campus Medical Complex is expected to include a hospital, outpatient medical and surgical facilities, and emergency care. It will augment UCI's 417-bed acute care hospital in Orange. The same cancer programs that are part of the Chao Family Comprehensive Cancer Center in Orange will be available in Irvine. The estimated completion date for the ambulatory portion is 2024, with the hospital completion in 2026.
"The complex will be designed with an eye toward education and clinical research to make sure the cutting-edge advantage we bring to our patients by having residents and fellows and students in our midst continues into the future," says Stamos. "Having learners in our environment keeps us all on our toes."
Scientists discover role of tumor stiffness in promoting cancer cell proliferation