Researchers develop a new technique to improve treatment for pancreatic cancer

An international team of scientists, headed by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and by HonorHealth Research and Innovation Institute, has comprehensively described the individual cells comprising the pancreatic cancer microenvironment—a crucial stage in developing new therapeutic options for patients suffering from this aggressive and difficult-to-treat disorder.

Researchers develop a new technique to improve treatment for pancreatic cancer
Image Credit: The Translational Genomics Research Institute.

The results of the study were recently published in the Genome Medicine scientific journal—a publication of Springer Nature.

The team employed a comparatively novel technique called single-cell sequencing to genetically detect both cell types and subtypes that occur in pancreatic tumors, and to also detect different cells present in the tumor’s stroma—a kind of substance surrounding the tumor that can conceal the cancer from the body’s  immune system.

Although single-cell transcriptomics has already been used to analyze the cellular composition of primary tumor tissues of pancreatic ductal adenocarcinoma (PDAC), the latest study also applied the technology to profile individual cells from dissociated primary tumors as well as biopsies of metastatic tissues, that is, cancerous lesions that have spread across the body from the primary tumor.

The research was performed in association with scientists from Samsung Medical Center and City of Hope, a leading independent research and treatment center dedicated to diabetes, cancer, and other fatal disorders.

The researchers sequenced primary tumors as well as core needle biopsies of metastatic lesions from PDAC patients 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.”

Haiyong Han, PhD, Study Senior Author and Professor, Molecular Medicine Division, The Translational Genomics Research Institute

Han is also the head of the Pancreatic Cancer Research Laboratory at TGen.

He continued “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.”

During the analysis, the researchers identified distinct cell types and subtypess, such as endothelial cells, immune cells, tumor cells, and cancer associated fibroblasts, and found that the expression levels of different genes in the individual cell populations correlated with the clinical outcomes in patients.

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.”

Erkut Borazanci, MD, MS, Medical Oncologist and Physician-Investigator, HonorHealth Research and Innovation Institute

Dr Borazanci is also a clinical associate professor at TGen and one of the study’s authors.

Pancreatic cancer is known to be an aggressive disease and is associated with a high mortality rate. In the United States, it is the third-leading cause of cancer death after lung and colorectal cancers.

In 2020, pancreatic cancer had a five-year survival rate of only around 10%, although that still indicates some amount of progress from the dismal 6% rate reported in 2014.

Using real-time techniques, the team will next use more sophisticated single-cell spatial transcriptomics analysis to further analyze the cellular links related to survival rates. A wider use of this novel technology could possibly guide the quest for novel agents to treat pancreatic cancer.

Source:
Journal reference:

Lin, W., et al. (2020) Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Genome Medicine. doi.org/10.1186/s13073-020-00776-9.

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