Metastatic pancreatic cancer: Mechanisms and detection (Review)

Abstract

Pancreatic cancer (PC) is a lethal malignancy. Its prevalence rate remains low but continues to grow each year. Among all stages of PC, metastatic PC is defined as late‑stage (stage IV) PC and has an even higher fatality rate. Patients with PC do not have any specific clinical manifestations. Most cases are inoperable at the time‑point of diagnosis. Prognosis is also poor even with curative‑intent surgery. Complications during surgery, postoperative pancreatic fistula and recurrence with metastatic foci make the management of metastatic PC difficult. While extensive efforts were made to improve survival outcomes, further elucidation of the molecular mechanisms of metastasis poses a formidable challenge. The present review provided an overview of the mechanisms of metastatic PC, summarizing currently known signaling pathways (e.g. epithelial‑mesenchymal transition, NF‑κB and KRAS), imaging that may be utilized for early detection and biomarkers (e.g. carbohydrate antigen 19‑9, prostate cancer‑associated transcript‑1, F‑box/LRR‑repeat protein 7 and tumor stroma), giving insight into promising therapeutic targets.

Keywords: biomarker; mechanism; pancreatic cancer metastasis; signaling pathway.

Figure 1.

Major signaling pathways in metastatic pancreatic cancer. EMT, epithelial-mesenchymal transition; ΝF-κΒ, nuclear factor-κ-light-chain-enhancer activated B cells; GDP, guanosine diphosphate; GTP, guanosine triphosphate; GAP, GTPase-activating protein; GEF, guanine nucleotide exchange factor; cGAS, cyclic GMP-AMP synthase; STING, stimulator of interferon genes; TBK1, TANK binding kinase-1; PI3K, phosphatidylinositol 3-kinase; IKK, inhibitor of ΝF-κΒ kinase; MEK, MAPK/ERK kinase; Erk, extracellular signal-regulated protein kinase; MLK3, mixed lineage kinase 3; TAK, transforming growth factor β-activated kinase; DLK, dual-leucine zipper kinase; P38 MAPK, P38 mitogen-activated protein kinase; MKK, MAP kinase kinase; SAPK/JNK, stress-activated protein kinase/c-Jun N-terminal kinase; MEKK, MEK kinase; BMK1, big MAP kinase 1.