The therapeutic value of targeting inflammation in gastrointestinal cancers

Abstract

Inflammation has been implicated in the initiation and progression of gastrointestinal (GI) cancers. Inflammation also plays important roles in subverting immune tolerance, escape from immune surveillance, and conferring resistance to chemotherapeutic agents. Targeting key regulators and mediators of inflammation represents an attractive strategy for GI cancer prevention and treatment. However, the targeting of inflammation in GI cancer is not straightforward and sometimes inflammation may contribute to tumor regression. We discuss the origins and effects of inflammation in GI cancer and how to target it successfully.

Keywords: cytokines; targeting therapy; tumor initiation; tumor promotion.

Figure 1. Role of inflammation in tumor initiation and progression

Inflammation can result in mutations and epigenetic changes that favor tumor initiation. ROS and RNI produced by activated inflammatory/immune cells, and DNA damaging toxins produced by carcinogenic pathogens, induce mutations and genomic alterations resulting in appearance of premalignant cells that proliferate and survive in response to cytokines produced by inflammatory immune cells.

Figure 2. Roles of NF-κB/STAT3/HIF-1α/AP-1 signaling pathways in GI cancers

Tumor promoting factors and cytokines stimulate immune/inflammatory cells to produce inflammatory mediators that activate key transcription factors, such as NF-κB, STAT3, HIF-1α, and AP-1. These transcription factor control numerous processes in pre-malignant and malignant GI epithelial cells, including survival, proliferation, angiogenesis, migration, invasion, and metastasis.