- Posted Tuesday September 29, 2020
TGen and HonorHealth investigators suggest this granular analysis could lead to better treatments for pancreatic cancer patients
SCOTTSDALE, Ariz. — Sept. 29, 2020 — Led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and by HonorHealth Research and Innovation Institute, an international team of researchers have described in detail the individual cells that comprise the pancreatic cancer microenvironment, a critical step in devising new treatment options for patients with this aggressive and difficult-to-treat disease.
The study results were published today in the scientific journal Genome Medicine, a publication of Springer Nature.
Researchers used a relatively new technique known as single-cell sequencing to genetically identify cell types, and subtypes, that occur in pancreatic tumors, and identify the various cells in the tumor’s stroma, a substance surrounding the tumor that can hide the cancer from the body’s immune system.
While single-cell transcriptomics has been used previously to study the cellular composition of primary tumor tissues of pancreatic ductal adenocarcinoma (PDAC), this study also used the technology to profile individual cells from dissociated primary tumors and biopsies of metastatic tissues, those cancerous lesions that have spread throughout the body from the primary tumor.
This study was carried out in collaboration with investigators from Samsung Medical Center and City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases. Primary tumors and core needle biopsies of metastatic lesions from PDAC patients were sequenced using the Chromium single cell RNA-Seq platform.
“Single-cell transcriptome analysis can offer important clinical insights on individual cell subpopulations and provide clues for developing novel therapeutic strategies for both targeted therapies and immunotherapies,” said Haiyong Han, Ph.D., a professor in TGen’s Molecular Medicine Division and head of the institute’s Pancreatic Cancer Research Laboratory.
“Understanding the diversity and complexity of the PDAC tumor and stromal compartments in individual tumors may help identify unique intervention points and potentially inform treatment and maintenance strategies for patients with advanced disease,” said Dr. Han, the study’s senior author.
Distinct cell types and subtypes were identified in the analysis, including tumor cells, endothelial cells, cancer associated fibroblasts, and immune cells, and the expression levels of various genes in the individual cell populations correlated with patient clinical outcomes.
“Working with our partners and colleagues by utilizing the technology of singe cell sequencing, we can continue to learn more about the biology of pancreas cancer. These insights may potentially help us determine more treatment options for our patients,” said Erkut Borazanci, M.D., M.S., a medical oncologist and physician-investigator at HonorHealth Research and Innovation Institute, a clinical associate professor at TGen, and one of the paper’s authors.
Pancreatic cancer is an aggressive disease that carries a high mortality rate. It is the third-leading cause of cancer death in the U.S., following lung and colorectal cancers. In 2020, the five-year survival rate for pancreatic cancer is only about 10%, though that represents progress from the dismal 6% rate in 2014.
Next, researchers plan to use more advanced single-cell spatial transcriptomics analysis to further investigate the cellular relationships related to survival rates using real-time methods. Broader use of this technology could potentially guide the search for new agents to treat pancreatic cancer.
This research was supported by: the National Foundation for Cancer Research; SU2C-CRUK-Lustgarten Foundation Pancreatic Dream Team Research Grant (SU2C-AACR-DT-20-16); Baylor Scott & White Research Institute (BSWRI) and Translational Genomics Research Institute (TGen) Collaboration in Oncology Research; and the Korean Health Technology R&D Project (HI14C2640).
The study — Single-Cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions — was published in the scientific journal Genome Medicine.
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About TGen, an affiliate of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
TGen Senior Science Writer
HonorHealth is a non-profit, local community healthcare system serving an area of 1.6 million people in the greater Phoenix area. The network encompasses six acute-care hospitals, an extensive medical group, outpatient surgery centers, a cancer care network, clinical research, medical education, a foundation and community services with approximately 12,300 employees, 3,700 affiliated physicians and 3,100 volunteers. HonorHealth was formed by a merger between Scottsdale Healthcare and John C. Lincoln Health Network. HonorHealth’s mission is to improve the health and well-being of those we serve. Learn more at HonorHealth.com
About HonorHealth Research and Innovation Institute:
HonorHealth Research and Innovation Institute is helping shape the future of medicine. We're finding cures and improving treatments in areas like gene therapy, early drug/device development, early detection and prevention of disease. Through our clinical trials and applied research, we’ve given hope and improved the lives of patients from all 50 states and 28 different countries around the globe. Our advanced technologies and cutting-edge treatment options are introducing tomorrow’s cures, today. For more information on oncology clinical trials for pancreatic cancer email [email protected].com or learn more at HonorHealth.com/research. Follow HonorHealth Research and Innovation Institute on Facebook, LinkedIn and Twitter @HRInstitute_AZ.