Inflammation and tumor progression: signaling pathways and targeted intervention

Abstract

Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

Dualistic role of autophagy in cancer progression

“…Many types of cells, such as inflammatory cells, can provide such signals. 55 Various inflammatory cells infiltrate the tumor reacting to necrosis, commonly seen in solid tumors, and produce different effects on the tumor. Natural killer (NK) cells and cytotoxic T lymphocytes generally have anti-metastatic influence, while macrophages in the tumor environment usually correlate with a poor clinical prognosis.…”

Molecular Mechanisms and Animal Models of HBV-Related Hepatocellular Carcinoma: With Emphasis on Metastatic Tumor Antigen 1

“…Accumulating evidence has demonstrated that inflammation plays an important role in the initiation, promotion, and progression of tumors [84]. HCC represents a classic paradigm of inflammation-linked cancer where various immune and inflammation factors, including T cells [55,85,86] and cytokines, as well as oxidative stress, contribute to hepatocarcinogenesis.…”

Long noncoding RNAs: fine-tuners hidden in the cancer signaling network

“…They participate in the transmission of cellular signals and are important for biological reactions and gene expression. Signaling pathways are extremely complex, and many signaling molecules are involved in cascade reactions, which are often regulated, directly or indirectly, by various types of molecules [ 8 ]. Emerging evidence shows that abnormal signal transduction is a key trigger and indicator for tumorigenesis and cancer progression and that lncRNAs, as versatile regulators, can shape the malignant phenotypes by activating or suppressing different signaling pathways [ 9 , 10 ].…”