Noncoding Rnas Emerging as Novel Biomarkers in Pancreatic Cancer

Abstract

Noncoding RNAs play important regulatory roles in diverse biological processes and their misregulation might lead to different diseases, including cancer. Previous studies have reported the evolving role of miRNAs as new potential biomarkers in cancer diagnosis, prognosis, as well as predictive biomarkers of chemotherapy response or therapeutic targets. In this review, we outline the involvement of noncoding RNA in pancreatic cancer, providing an overview of known miRNAs in its diagnosis, prognosis and chemoresistance. In addition, we discuss the influence of non-coding RNAs in the metastatic behavior of pancreatic cancer, as well as the role of diet in epigenetic regulation of non-coding RNAs in cancer, which can, in turn, lead the development of new prevention’s techniques or novel targets for cancer therapy.

State of the Art for Metastatic Pancreatic Cancer Treatment: Where Are We Now?

“…Moreover, even if less common, alterations in DNA repair, WNT signaling, chromatin, RNA processing and Notch signaling have been studied and targeted in several clinical trials. K-RAS mutations are found in 90% of PDAC, CDKN2A mutations in 63%, SMAD4 in 33% and TP53 in 26% (1)(2)(3)(4)7). Most of these mutations or altered signaling pathways have been targeted in clinical trials by stem cell inhibitors, CDK4/6 inhibitors, insulin-like growth factor inhibitors, tropomyosin receptor kinase inhibitors, and STK11 pathway inhibitors.…”

“…Most of these mutations or altered signaling pathways have been targeted in clinical trials by stem cell inhibitors, CDK4/6 inhibitors, insulin-like growth factor inhibitors, tropomyosin receptor kinase inhibitors, and STK11 pathway inhibitors. Moreover, exploring the efficacy of drugs targeting stroma, macrophages or metabolism is an interesting approach for PDAC treatment (1)(2)(3)(4)7).…”

“…Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, with less than 10% of patients being alive at 5 years after diagnosis (1)(2)(3)(4). Radical surgical resection remains the only possibility of cure for PDAC patients, however, even after radical removal, the probability of relapse is high.…”

“…Radical surgical resection remains the only possibility of cure for PDAC patients, however, even after radical removal, the probability of relapse is high. Five-year survival rates after surgical resection and adjuvant chemotherapy are approximately 20%, and the average survival of resected patients is between 12 and 20 months (1)(2)(3)(4). Around half of the PDAC patients are diagnosed with metastatic disease, mainly due to nonspecific symptoms.…”

“…These patients should undergo systemic anticancer treatment with palliative intent. Unfortunately, chemotherapy prolongs life by only few months, and PDAC chemoresistance renders most drugs ineffective (1)(2)(3)(4). Despite extensive clinical trials, most cytotoxic or targeted therapies failed to demonstrate efficacy, and the prognosis of PDAC has only slightly improved over the past 20 years.…”