Building towards Precision Oncology for Pancreatic Cancer: Real-World Challenges and Opportunities

Abstract

The advent of next-generation sequencing (NGS) has provided unprecedented insight into the molecular complexity of pancreatic ductal adenocarcinoma (PDAC). This has led to the emergence of biomarker-driven treatment paradigms that challenge empiric treatment approaches. However, the growth of sequencing technologies is outpacing the development of the infrastructure required to implement precision oncology as routine clinical practice. Addressing these logistical barriers is imperative to maximize the clinical impact of molecular profiling initiatives. In this review, we examine the evolution of precision oncology in PDAC, spanning from germline testing for cancer susceptibility genes to multi-omic tumor profiling. Furthermore, we highlight real-world challenges to delivering precision oncology for PDAC, and propose strategies to improve the generation, interpretation, and clinical translation of molecular profiling data.

Keywords: biomarkers; pancreatic cancer; precision oncology; targeted therapy.

Figure 1

Framework outlining strategies to facilitate implementation of PDAC precision oncology in clinical care. Dotted lines highlight the value of generating preclinical models in parallel, if such platforms are available. Double-headed arrow depicts the potential use of preclinical models to (1) inform precision oncology trial designs and (2) gain mechanistic understanding of treatment responses and acquired treatment resistance observed in biomarker-driven clinical trials. GC, genetic counselling; GT, germline testing; MTB, molecular tumor board; AI, artificial intelligence.