UT MD Anderson Cancer Center
Spatial omics profiling to assess the impact of aging on the normal and neoplastic pancreas
Overview
Aim: Cancer Biology
Pancreatic cancer is the 3rd most common cause of cancer-related deaths in the United States. While the median age of onset for pancreatic cancer is in the late 60s, there has been a striking and worrisome increase in the annual incidence of early-onset pancreatic cancer (EOPC), defined as cancer in individuals less than 50 years of age, with recent trends showing an 18% increase of EOPC in just the past decade. Previous studies have examined how DNA abnormalities (mutations) differ between EOPC and usual-onset pancreatic cancer (UOPC), but these at best explain only a minority of cases. Thus, the underlying bases for increasing EOPC incidence remain largely unknown.
We hypothesize that EOPC represents a disease of accelerated aging within the pancreatic “soil” that creates a fertile milieu for cancer development. Therefore, the first step to addressing the enigma of EOPC begins with creating a comprehensive molecular “atlas” that goes beyond the tumor itself, but also examines the proverbial “soil” (adjacent uninvolved pancreas).
We will integrate multiple analytes (DNA, RNA, and protein alterations) in an unbiased manner to create the first molecular atlas comparing EOPC versus UOPC, including changes within the surrounding pancreas. Notably, we will utilize a unique series of age-matched pancreas samples obtained from cancer-free organ donors as pivotal controls for how “normal aging” might differ from “accelerated aging” we anticipate in EOPC. This study will provide crucial foundational data for elucidating the mechanisms underlying EOPC.