A look back at notable events and achievements at UNC Lineberger Comprehensive Cancer Center the past year.

UNC Lineberger Comprehensive Cancer Center’s faculty were at the forefront of a many new efforts to fight, prevent and understand cancer in 2018. Projects launched or completed in the year included efforts to use the immune system to fight cancer, to better prevent cancer through screening, and to understand the disease at the most basic biological levels using genetic sequencing. The research excellence was validated, in part, by the millions of dollars in grant funding awarded to support the work, the high volume of prestigious scientific publications, and the placement of UNC Lineberger faculty in key leadership positions with top national cancer agencies and organizations.

In terms of clinical care delivery, the cancer center is “second to none,” said UNC Lineberger Director H. Shelton Earp, MD, speaking at the center’s annual scientific retreat earlier in the year. Earp highlighted the three-fold growth in new patients to the N.C. Cancer Hospital since it opened in 2009, and celebrated the recruitment and retention of clinical faculty in surgical oncology, radiation oncology, pediatric oncology, cancer outcomes research, and other areas.

Here is a look at some of the top stories from 2018.

Researchers help map the cancer genome, generate key insights

The Cancer Genome Atlas was a national effort backed by the National Cancer Institute and National Human Genome Research Institute to understand how changes in our genes and differences in how they are expressed are involved in cancer.

UNC Lineberger researchers were involved in the project from the beginning. At the project’s culmination, Katherine Hoadley, PhD, assistant professor in the UNC School of Medicine Department of Genetics, was lead and co-corresponding author of a study that analyzed 10,000 tumors, across 33 different human cancer types such as breast, lung, colon, or ovarian cancer. The researchers identified an expanded classification for cancers based on genetic and genomic alterations. UNC Lineberger researchers were authors on more than 20 papers published in April at TCGA’s conclusion.

As a whole, TCGA has helped create a dictionary of genetic alterations in cancers that other researchers can use to aid future efforts to better understand individual tumor types. The data is publicly available, and next to data from the Human Genome Project, data from TCGA likely represent the most widely utilized human genomic resource.

Former patient donates $10M to further blood cancer research

Etteinne “ET” and W. G. Champion “Champ” Mitchell of New Bern, North Carolina, donated $10 million to create a new fund supporting ground-breaking research in blood cancer at UNC Lineberger, including lymphoma, leukemia and myeloma research in October.

Champ Mitchell was treated for stage IV non-Hodgkin lymphoma at N.C. Cancer Hospital, the clinical home of UNC Lineberger. The care he received inspired the Mitchells to create the Champ and ET Mitchell Fund for Blood Cancer Research. This fund will accelerate research, ultimately improving the lives of future patients.

“Every day, 151 fellow North Carolinians learn they’re facing a daunting battle against a deadly disease. And I know from personal experience, it’s not a fight you can or should do alone,” Champ Mitchell said.

Study shows promise for fighting relapsed blood cancer with CAR-T immunotherapy, chemotherapy

Although Hodgkin lymphoma is a generally curable type of cancer, there is a small percentage of patients whose disease does not respond to therapy. UNC Lineberger researchers launched a clinical trial using genetically modified immune cells, called chimeric antigen receptor (CAR) T-cells, along with chemotherapy, to fight relapsed or refractory Hodgkin lymphoma.

Natalie Grover, MD, reported at the American Society of Hematology Annual Meeting in December promising preliminary results from the phase I trial that used two particular types of chemotherapy prior to treatment with the CAR-T immunotherapy.

Grover said their work will be ongoing to try to improve outcomes from the investigational treatment, including through another clinical trial that is designed to evaluate a mechanism for helping to recruit CAR T-cells to tumor sites.

“This study shows this is worth pursuing further, and the next step is to improve on this investigational therapy,” said Grover, an assistant professor in the UNC School of Medicine Division of Hematology/Oncology.

Researchers take a step toward highly personalized immune treatments
A new approach could lead to more targeted, and safer, transplants for patients with leukemia.

A scientific team led by UNC Lineberger’s Ben Vincent, MD, Paul Armistead, MD, PhD, have published findings from a study that could aid in the development of immune-based treatments that are tailored to individual leukemia patients who are undergoing stem cell transplantation.

In the journal Blood Advances, researchers reported they validated a method of using genetic sequencing and computer software to predict which patient sequences resulted in unique surface markers, or minor histocompatibility antigens, on the surface of cancer cells. They confirmed this approach in a group of patients with myeloid leukemia who were undergoing stem cell transplant.

They envision that potentially, they could use their predictions to engineer donor immune cells to specifically target the cancer cell antigens for that patient. At the same time, the approach could prevent graft-versus-host disease, in which the donor’s immune cells attack healthy tissues.

By sending tests in the mail, researchers boost colorectal cancer screening

Colorectal cancer screening has proven effective in reducing cancer deaths. Yet, researchers report too few people are getting screened. Among patients who are insured, people with Medicaid have the lowest rates of colorectal cancer testing.

In the journal Cancer, UNC Lineberger’s Alison Brenner, PhD, MPH, Stephanie Wheeler, PhD, MPH, and their colleagues reported in July they increased screening rates by mailing colorectal cancer screening tests directly to patients insured by Medicaid. Working in collaboration with the Mecklenburg County Health Department in Charlotte, the researchers examined the impact of targeted outreach to more than 2,100 people insured by Medicaid who were not up-to-date with colorectal cancer screening.

The project resulted in a nearly 9 percentage point increase in screening rates for patients who received a screening kit in the mail compared with patients who just received a reminder.

Researchers identify molecular target for brain cancer, develop immunotherapy approach to attack it

An international team of researchers led by UNC Lineberger’s Gianpietro Dotti, MD, reported in the journal Science Translational Medicine in March they have genetically engineered cancer-killing immune cells that can hunt brain tumors displaying a new molecular target that is highly prevalent on brain cancer cells.

Based on the data from their early, preclinical studies the researchers believe their approach holds promise for a new immunotherapy treatment for glioblastoma, which is the most lethal primary brain tumor.

Could reading our circadian clocks according to DNA repair optimize chemotherapy?

UNC Lineberger scientists led by Nobel laureate Aziz Sancar, PhD, developed a way to measure the repair of DNA damage caused by cisplatin, a common anti-cancer drug.  They used this technique to measure DNA repair after cisplatin treatment over the course of an entire 24-hour circadian cycle throughout an entire genome of a mammal.

Through this analysis, which was published in the Proceedings of the National Academy of Sciences in May, they found which genes were repaired, where exactly, and when – a discovery that could lay the groundwork for a more precise use of anti-cancer drugs.

Breast cancer risk increases after childbirth

The risk of breast cancer in younger women is low overall, but a large-scale analysis co-led by a UNC Lineberger’s Hazel Nichols, PhD, found that younger women who have recently had a child may have a higher risk of breast cancer than their peers of the same age who do not have children. The study was published in the Annals of Internal Medicine in December.

“What most people know is that women who have children tend to have lower breast cancer risk than women who have not had children, but that really comes from what breast cancer looks like for women in their 60s and beyond,” said UNC Lineberger’s Hazel B. Nichols, PhD, an assistant professor in the UNC Gillings School of Global Public Health Department of Epidemiology. “We found that it can take more than 20 years for childbirth to become protective for breast cancer, and that before that, breast cancer risk was higher in women who had recently had a child.”

The study’s findings could be used to develop better breast cancer risk prediction models to help inform screening decisions and prevention strategies, Nichols said.

UNC Lineberger hosts delegation from Malawi
A team of Malawian health and government officials convened at UNC Lineberger to meet with health and university leaders, researchers and clinical staff across three days in June to prepare for the opening of the first dedicated cancer center in Malawi.

UNC Lineberger physicians and researchers have been collaborating with Malawian health leaders to improve clinical care and to conduct cancer research in the country in sub-Saharan Africa as part of UNC Project-Malawi, a collaboration launched in 1990 to help with HIV management.

As HIV survival rates have improved, and due to other factors, cancer has emerged as a growing health problem in the country. In 2014, the Malawi Cancer Consortium was launched with funding from the National Cancer Institute to help fight cancer, and AIDS-linked cancers in particular.

Researchers publish a book on helping widowed fathers cope after cancer
Seven years after launching a support group for widowed fathers after losing their spouses to cancer, UNC Lineberger’s Donald Rosenstein, MD, and Justin Yopp, PhD, published in January “The Group: Seven Widowed Fathers Reimagine Life,” a book that recounts the lessons the widowed fathers learned in responding to loss and grief.

Yopp said the idea to write the book came, in part, from the fathers wanting to use their experiences to help others dealing with loss and grief.

“It became increasingly important to these men that the work we were doing, and they were helping us do, would help other people,” said Yopp, who is an associate professor of psychiatry and a member of the UNC Lineberger Comprehensive Cancer Support Program. “If the pain they’ve experienced could, in some way, help someone else, that was meaningful to them, and that was meaningful to us, too.”

 
Katherine Hoadley, PhD W.G. Champion “Champ” and Etteinne “ET” Michell
Natalie Grover, MD Ben Vincent, MD, and Paul Armistead, MD, PhD
Alison Brenner, PhD, MPH, and Stephanie Wheeler, PhD, MPH Gianpietro Dotti, PhD
Aziz Sancar, PhD Hazel Nichols, PhD
Malawian health officials Donald Rosenstein, MD, and Justin Yopp, PhD