8 June 2021

lncRNAs: potential therapeutic targets and biomarkers for pancreatic cancer?

Montes, M., & Arnes, L. (2021). lncRNAs: potential therapeutic targets and biomarkers for pancreatic cancer? Expert Opinion on Therapeutic Target. doi: 10.1080/14728222.2021.1938541

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths with limited therapeutic opportunities 1. Recently, molecular analysis uncovered inter- and intra-tumoral heterogeneity, signalling pathways commonly upregulated in PDAC and revealed strategies for patient stratification 2. Despite a better understanding of the molecular drivers and the signalling pathways dysregulated in PDAC, only a low fraction of patients has druggable alterations. However, cancer genome studies have been focused on mutations and gene expression analysis of protein-coding genes, which represents less than 2% of the genome. Within the non-coding genome, there is increasing evidence that a subset of non-coding RNAs, termed long non-coding RNAs (lncRNAs), are involved in cancer biology 3. Many lncRNAs are tissue- and cell type-specific both in normal tissues and in tumours, making them excellent candidates for drug targeting as well as diagnosis 4. Furthermore, the number of lncRNAs may exceed the number of coding genes, which can dramatically widen the repertoire of druggable molecules. Here, we will discuss diagnostic and therapeutic opportunities based on lncRNA expression and RNA-targeting approaches in pancreatic cancer. We argue that lncRNAs are key regulators of phenotypic adaptations in cancer initiation and resistance to therapy. The emerging of nucleic acid therapeutics provides a viable approach to develop targeted therapies aimed at lncRNAs to halt the progression of PDAC