June 19, 2018:
Big Ten cancer centers are making strides and tackling some of the toughest questions in cancer research. In this month’s edition of Across the Consortium, we highlight advances in prostate cancer, breast cancer, head and neck cancer, multiple myeloma, bladder cancer, colorectal cancer, and new technologies and discoveries that could improve outcomes across many cancers. Behind these advances in research at Big Ten cancer centers are academic physicians and scientists who are not only brilliant in their fields, but also committed to research mentorship and disease prevention.
University of Illinois Cancer Center
Caucasian men accounted for about 106 new cases of prostate cancer per 100,000 men for the years 2011-2015. For African American men, that number jumped to nearly 179 per 100,000. University of Illinois Cancer Center member Alan Diamond has received a U.S. Department of Defense grant to study the accuracy of his hypothesis that the gene SELENOF is a contributing factor in the disparity.
The combination of genetics and environmental factors likely play a role in why African American men experience a higher incidence of prostate cancer, as well as having a worse clinical outcome, said Diamond, PhD, pathology professor at the University of Illinois at Chicago College of Medicine. In prior studies, Diamond has compared the amount of SELENOF in prostate cancer to normal tissue, and the gene is expressed at significantly lower levels in African American men compared to Caucasian men.
Indiana University Melvin and Bren Simon Cancer Center
A few decades ago, Harikrishna Nakshatri, PhD, was practicing veterinary medicine in India. After traveling the world to study hormonal signaling and earning a PhD in molecular biology, he’s now using that knowledge to research new ways to fight breast cancer.
“From the very beginning, I’ve been interested in how the hormones function in the body, because they are small molecules,” said Dr. Nakshatri. “I used to practice large animal medicine, and hormonal signaling is critical for cows to be productive, so that drew my curiosity and now I’m working on hormonal breast cancer.”
University of Iowa Holden Comprehensive Cancer Center
A small molecule called GC4419 administered before intensity-modulated radiotherapy (IMRT) may reduce the duration and incidence of severe oral mucositis (OM) in patients with oral cavity (OC) and oropharyngeal (OP) cancers, according to the results of a randomized phase IIb trial presented during the “Head and Neck Cancer” Oral Abstract Session, held June 3 (Abstract 6006).
Although IMRT minimizes radiation dose to normal tissue, approximately 70% of patients receiving IMRT and cisplatin will develop severe (grade 3 or 4) OM. Patients with these adverse events develop ulcers and require a liquid diet (grade 3) or intravenous/tube feeding (grade 4), based on the World Health Organization OM grading system.
GC4419, which is a manganese superoxide dismutase mimetic, “provides a clinically meaningful reduction in severe OM duration, incidence, and severity,” Carryn M. Anderson, MD, of University of Iowa Hospitals and Clinics, said.
University of Michigan Rogel Cancer Center
Cancer is crafty. To survive and thrive, tumors find a way of thwarting our body’s natural systems.
By looking at these systems, researchers at the University of Michigan Rogel Cancer Center have discovered that tumor cells reprogram metabolic pathways to gain control over a type of immune cell that allows cancer growth.
Myeloid-derived suppressor cells live in the tumor microenvironment and work to block cancer immunity. They also encourage a stem cell-like growth that’s linked to more aggressive cancer. Patients with a lot of these suppressor cells typically have worse outcomes. Essentially, their immune system isn’t strong enough to fight against the tumor.
Michigan State University Breslin Cancer Center
Anna Moore has joined Michigan State University as the director of the Precision Health Program and assistant dean of the College of Human Medicine.
Moore was previously professor of radiology at Massachusetts General Hospital/Harvard Medical School.
As director of MSU’s Precision Health Program, Moore’s vision is to lead health care away from simply treating symptoms to restoring health before symptoms occur. Moore said this can be done by conducting genetic screens early in life to look for complex genetic factors and assess disease risk. With this risk assessment a person can be monitored over their lifetime for early indicators or symptoms and treated as early as possible.
Masonic Cancer Center, University of Minnesota
Nearly 80 million Americans – one out of every four people – are infected with human papillomavirus (HPV). And of those millions, more than 31,000 will be diagnosed with an HPV-related cancer this year. Despite those staggering figures and the availability of a vaccine to prevent the infections that cause these cancers, HPV vaccination remains low in the United States.
The Masonic Cancer Center has partnered with 69 other National Cancer Institute (NCI)-designated cancer centers to issue a statement urging for increased HPV vaccination and screening to eliminate HPV-related cancers, starting with cervical cancer. These institutions collectively recognize insufficient vaccination as a public health threat and call upon the nations’ physicians, parents and young adults to take advantage of this rare opportunity to eliminate several different types of cancer in men and women.
Fred & Pamela Buffett Cancer Center (University of Nebraska)
Multiple myeloma is the second most common blood cancer in the United States, with an estimated 30,280 new patients diagnosed in 2017. Over the last several decades, with the development of newer therapies, average survival of myeloma patients has risen to greater than ten years on average. Nevertheless, regardless of the initial response to therapy, most myeloma patients will experience disease progression at some point in their disease course, requiring novel approaches to control disease progression. Hence, learning about the mechanisms of myeloma resistance or failure of response to common myeloma drugs is of great interest and importance.
At Nebraska Medicine/UNMC, we are committed to continuous discovery and learning about the disease mechanisms that will allow us to prolong the use of cornerstone myeloma drugs such as proteasome inhibitors (e.g bortezomib/velcade or carfilzomib/kyprolis). Our past experience has taught us that not all patients with myeloma will respond favorably to proteasome inhibitors, and those that do, are predicted to eventually develop resistance to this type of drug at some point during the treatment of their disease.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Using blood samples to count circulating tumor cells may help to classify metastatic breast cancer patients according to their tumors’ aggressiveness, raising the possibility of more tailored treatments, with fewer severe side effects, for those whose advanced cancers are likely to be less aggressive.
These findings were presented in the poster, “The impact of circulating tumor cells (CTCs) detection in metastatic breast cancer (MBC): Implications of “indolent” stage IV disease (Stage IVindolent),” at the recent 2018 American Society of Clinical Oncology (ASCO) Meeting in Chicago.
Circulating tumor cells, or CTCs, are cancer cells shed from the primary tumor or its metastases that circulate in the blood or lymphatic system.
Penn State Cancer Institute
Mutations in genes that help repair damage to DNA may aid in predicting the prognosis of patients with bladder and other related cancers, according to researchers.
The researchers found that bladder cancer patients who had mutations in their ATM or RB1 genes — proteins that help repair DNA damage when they’re functioning normally — tended not to live as long as patients without the mutations.
Dr. Monika Joshi, assistant professor of medicine at Penn State Cancer Institute, said that as researchers try to design better treatments for cancer patients, it’s important for them to find biomarkers that can help researchers understand the differences between patients and their prognoses.
Purdue University Center for Cancer Research
Andy Tao tempered his expectations when his lab started an experiment to see whether they could identify phosphorylated proteins in blood.
Phosphorylation — the addition of a phosphate group to a protein — is often a precursor to cancer cell formation, but detecting the process would only be half the battle. They needed to correctly identify the phosphorylated proteins in the blood of patients known to have cancer.
“My student, Blair Chen, got the data and immediately came to my office,” Tao says. “She detected over a thousand phosphorylated proteins from 1 milliliter of plasma in a single experiment. She was shocked, and I was totally overwhelmed.”
For years, scientists have searched for biomarkers, measurable substances in the body that correlate with the presence of disease or infection. The promise is the ability to detect cancer, viruses, heart disease and other maladies through a simple blood draw or urine analysis. But success has been elusive.
Rutgers Cancer Institute of New Jersey
Targeted therapy with anti-VEGF and anti-EGFR antibodies both improve outcomes when added to chemotherapy in the treatment of colorectal cancer. However, some previous studies suggested the combination of the two antibodies may have a negative interaction. Those studies were done without selecting patients for KRAS mutations. Investigators from the ECOG-ACRIN Cancer Research Group led by Howard S. Hochster, MD, FACP, associate director for clinical research and director of gastrointestinal oncology at Rutgers Cancer Institute of New Jersey, wanted to explore the anti-VEGFR antibody ramucirumab in second-line treatment.
They examined whether ramucirumab improved activity of the combination of the chemotherapy drug irinotecan with the anti-EGFR antibody cetuximab for those patients previously treated with FOLFOX or CAPOX and bevacizumab whose disease began to progress. The work focuses on a form of colorectal cancer that has normal KRAS genes (about 60 percent of metastatic colorectal cancer). Previous research has shown that the antibodies that block the EGFR antibody have activity against this type of colorectal cancer, but not when the tumor harbors KRAS mutations. Another question explored was the effect of a second anti-VEGF antibody (ramucirumab) if patients had previously received bevacizumab.
University of Wisconsin Carbone Cancer Center
The University of Wisconsin Carbone Cancer Center took part in a large clinical trial to determine the best treatment for women with early stage breast cancer. The findings, announced in early June, showed the majority of women with the most common form of early breast cancer do not need chemotherapy as long as they take medications that block estrogen. A test on tumors removed during surgery can show which women need chemotherapy and which can safely skip it.
Carbone Cancer Center breast cancer oncologist Dr. Kari Wisinski answers some questions on these new findings.
Information for this story was compiled from Big Ten CRC member websites, news releases, and social media.
About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.
About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to almost 9,500 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.
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