The AACR Annual Meeting 2019 features the theme “Integrative Cancer Science • Global Impact • Individualized Patient Care.” That theme provided the structure for Monday’s plenary session, when cancer researchers representing three continents, four cancer types, and diverse areas of interest took the stage.
Monday’s plenary, titled “Clinical and Translational Research in Diverse Populations,” was moderated by Lisa A. Newman, MD, MPH, of NewYork-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine. A renowned breast cancer researcher, Newman has visited numerous African nations to conduct research and to train local physician-scientists. She said Monday’s plenary was designed to showcase the global burden of cancer, and the disparities in cancer outcomes in many corners of the world.
“Many populations internationally, as well as communities right here in the United States, suffer a disproportionate mortality burden because of unequal access to care,” she said. Monday’s first speaker described how that unequal access affects cancer incidence and mortality in Nigeria.
High-tech and low-tech cancer strategies in Nigeria
Olusegun I. Alatise, MSc, is an oncologist and senior lecturer at Obafemi Awolowo University Teaching Hospitals Complex in Nigeria, with a focus in colorectal cancer. He said that while colorectal cancer incidence and mortality rates have declined or stabilized in some parts of the world, they are rising in lower- and middle-income countries (LMICs). He said increasingly sedentary lifestyles may be one factor in rising rates. And ironically, improved health care has allowed more people in LMICs to live to elderly ages, when colorectal cancer is more likely to occur.
In recent years, he has taken part in the African Research Group for Oncology, a consortium of several Nigerian hospitals and Memorial Sloan Kettering Cancer Center in New York City. The consortium has established a colorectal cancer database in Nigeria, helping researchers gain valuable information about patients in a nation that has typically not had comprehensive cancer registries.
Alatise said that with the backing of the consortium, researchers have been able to screen colorectal cancer patients for mutations that can be targeted by existing therapeutics. For example, he said Nigerian patients appear more likely than North American patients to have high microsatellite instability (MSI), a quality that often makes tumors more responsive to immune checkpoint inhibitors.
While tumor testing holds great promise, Alatise said he and his colleagues also focus on “low-tech” ways of improving colorectal cancer detection. They publicize common symptoms of the disease, such as rectal bleeding and weight loss, and with a grant from the National Institutes of Health, are working to develop a urine metabolomics test as a less-invasive alternative to colonoscopies.
“It will take high-tech and low-tech solutions to improve outcomes,” Alatise said.
Alternative RNA splicing as a source of prostate cancer disparities
“There are multifactorial contributors to cancer disparities: lifestyle, social, structural, and biological. I have had the privilege of working in all these areas, but today, I am here to talk about some of the biological factors that underscore cancer health disparities,” said Steven R. Patierno, PhD, deputy director of the Duke Cancer Institute in Durham, North Carolina.
Patierno’s recent research has focused on alternative RNA splicing, a biological process that affects about 90 percent of human genes. This process provides a way for cells to have a more diverse array of proteins than would be possible if each gene could encode only one protein. It has also emerged as a source of heterogeneity in cancer, as detailed in a recent Cancer Research Catalyst post.
“Splicing itself has been traditionally overlooked in neoplasia,” he told the crowd on Monday. “We have increasing evidence that alternative splicing promotes tumor aggressiveness and drug resistance in African-American patients.”
Patierno discussed how his lab has been using CRISPR technology to manipulate the splicing process. He and colleagues believe that splice variants could ultimately serve as biomarkers. They developed models of prostate cancer that bear specific splice variants and are attempting to target the variants using small molecules.
“Alternative RNA splicing is potentially a major source of untapped molecular targets in precision oncology and cancer disparities,” Patierno said.
Breast cancer disparities: The DARC side
Although breast cancer is more likely to be diagnosed in white women than in African-American women, mortality rates from the disease are higher among African-American women. This trend has intensified in the past few decades, said the morning’s third presenter, Melissa B. Davis, PhD, of the Englander Institute for Precision Medicine at Weill Cornell Medicine.
Researchers have some information on why survival rates differ between races. White women have historically been more likely to have a form of breast cancer that responds to hormone therapies or aromatase inhibitors. African-American women have been more likely to develop triple-negative breast cancer, which does not respond to hormone therapy.
Davis’s research seeks more information from the human genome.
“Genomics is helping quicken the pace of research,” Davis said. “We should be able to identify why we have these differential outcomes.”
In recent years, a major focus of Davis’s work has been a chemokine receptor known as the Duffy Antigen Receptor for Chemokines (DARC). Women of African descent often carry a mutation that removes DARC expression from red blood cells. This mutation, known as the Duffy-Null allele, appears to promote tumor progression and metastasis, Davis said.
“The Duffy-Null allele in people of African ancestry is associated with triple-negative breast cancer risk.” Davis said. “Overall, it is associated with more aggressive cancers and may contribute to the higher breast cancer mortality among African American women.”
Davis pointed out that discoveries like this can only take place if sources of data such as The Cancer Genome Atlas enroll diverse patient populations.
“We just have to make sure to include all populations in our research,” Davis said, to ensure that people of all racial and ethnic backgrounds benefit equally from advances in cancer research.
Clues to a rare liver cancer are found in nature
Liver cancer is a fairly uncommon type of cancer, and a subtype that affects the bile ducts, cholangiocarcinoma, is both rare and deadly, said the final plenary speaker, Bin Tean Teh, MD, PhD, deputy director of research at National Cancer Centre Singapore.
Global rates of cholangiocarcinoma are concentrated in Asia. Teh explained that the major risk factor for this cancer type is infection with parasitic worms called liver flukes, which live in the fresh waters of Southeast Asia.
“People eat fish that has been infected with the liver flukes, then they grow in the bile duct system,” Teh explained. “Ultimately, the infection can lead to cholangiocarcinoma.”
Recent research suggests that the fluke might not bear sole responsibility for the higher rates of cholangiocarcinoma in Asian populations. Teh said an herbal carcinogen called Aristolochic acid has been implicated as a risk factor for the disease. This herb is commonly known as birthworts, pipevines, or dutchman’s pipes, and it has been banned in some countries.
“This is yet another risk factor that has emerged for liver cancer in Asia,” Teh said. Genomic and epigenomic analysis of liver cancers with distinct etiologies can help tailor treatments, he added.
Newman thanked all four speakers and the AACR for emphasizing diversity in this year’s program.
“The AACR has always been ahead of the curve in presenting cutting-edge research,” she said. “Thank you for giving us the opportunity to look at international patterns of cancer and the source of cancer health disparities.”
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