Dr Kamath on the Rationale for Investigating Early-Onset vs Average-Onset PDAC

Suneel Kamath, MD, assistant professor, medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, discusses the rationale for conducting an investigation into the tumor microbiome differences between early-onset and average-onset pancreatic ductal adenocarcinoma (PDAC), highlighting next steps with this research.

Findings from this investigation were presented at the 2024 ASCO Annual Meeting. The study examined resected PDAC specimens classified by age at diagnosis, using metagenomic sequencing to identify bacterial and fungal microbiomes. The key findings indicated that early-onset PDAC had higher bacterial alpha diversity, and average-onset PDAC had higher fungal alpha diversity. Furthermore, there were significant differences in beta diversity and the relative abundance of top genera between early- and average-onset disease, highlighting distinct microbiome signatures.

The rationale behind the study was based on the observation that the incidence of several cancers, including pancreatic cancer, has substantially increased among younger people over the past few decades, Kamath begins. Although significant research has focused on this trend in cancers such as colorectal cancer, pancreatic cancer has received less attention, he says, adding that one goal of this study is to understand why more young people are developing pancreatic cancer now compared with in previous decades.

It is important to identify specific microbiome- and immune-based signatures of early-onset PDAC, Kamath continues. Investigators hope to use this information in 2 ways. First, these findings may be used to develop screening tests that can identify unique signatures of early-onset pancreatic cancer and distinguish patients with this disease from healthy individuals, enabling effective screening of younger populations, he reports. The microbiome is easily measured in plasma, stool, and other specimens, making it convenient to use for screening purposes, Kamath elucidates.

Second, investigators aim to develop more personalized treatments for patients with early-onset pancreatic cancer, who often present with advanced metastatic disease and poor outcomes, according to Kamath. By achieving early detection and creating tailored interventions, researchers hope to improve treatment outcomes for this disease, he concludes.