Investigating Cellular Communication in the Tumor Microenvironment in Pancreatic Cancer

Abstract public domain (NIH RePORTER)

PROJECT ABSTRACT Pancreatic cancer is a deadly malignancy that is highly resistant to current therapies. Further, this disease does not impact all racial groups equally. Black African American (BAA) individuals are 20% more likely to develop pancreatic cancer, and have worse outcomes compared to White patients. Even controlling for numerous factors such as environment, socioeconomic status, health behaviors, and other common causes of disparities, these differences remain. Thus, it is critical to address underlying biological mechanisms of racial disparities. We have previously shown that the developmental signaling pathway SLIT-ROBO is globally down-regulated in pancreatic cancer compared to normal pancreas. Our single cell RNA sequencing data show SLIT ligands are produced by pericytes and cancer associated fibroblasts, while ROBO receptors are more broadly distributed across endocrine, fibroblasts, and blood vessels. Prior studies and our preliminary data lead us to hypothesize that this pathway plays a tumor- suppressive role in pancreatic cancer. However, it is unknown if this loss is observed equally across different racial groups. Unfortunately, our current single cell RNA sequencing atlas build from published studies is only 4 BAA patients and 196 White patients. Here we propose to generate key new single cell RNA sequencing data from a diverse cohort of pancreatic cancer patients (n=75 White and n=75 BAA) to address this urgent and unmet need.

Public health relevance public domain (NIH RePORTER)

PROJECT NARRATIVE Pancreatic cancer is a deadly malignancy with a 5 year survival rate of 13%. There is a 20% increased incidence and worse outcomes in Black African Americans (BAA) pancreatic cancer patients, compared to White patients, however the underlying biological mechanisms that drive this remains unknown. Our data show that SLIT-ROBO signaling is lost during pancreatic cancer progression. In this proposal we aim to significantly expand the current diversity of single cell RNA sequencing data of human pancreatic cancer patients to uncover potential underlying biological differences, including mapping expression of SLIT-ROBO signaling components in each cellular compartment across different racial groups.