Cancer and inflammation

Abstract

The relationship between inflammation and cancer has been recognized since the 17th century (6), and we now know much about the cells, cytokines and physiological processes that are central to both inflammation and cancer (39, 62, 66–68, 86, 92, 125). Chronic inflammation can induce certain cancers (11, 14, 27, 59, 61, 76, 79, 82), and solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination (7, 17, 67, 96). Consequently, inflammatory pathways have been targeted in attempts to control cancer (22, 46, 47). Inflammation is a central aspect of the innate immune system’s response to tissue damage or infection, and also facilitates the recruitment of circulating cells and antibodies of the adaptive immune response to the tissue. Components of the innate immune response carry out a robust, but sometimes overly-conservative response, sacrificing specificity for the sake of preservation. Thus, when innate immunity goes awry, it can have profound implications. How the innate and adaptive immune systems cooperate to neutralize pathogens and repair damaged tissues is still an area of intense investigation. Further, how these systems can respond to cancer, which arises from normal “self” cells that undergo an oncogenic transformation, has profound implications for cancer therapy. Recently, immunotherapies that activate adaptive immunity have shown unprecedented promise in the clinic, producing durable responses and dramatic increases in survival rate in patients with advanced stage melanoma (84, 119, 121). Consequently, the relationship between cancer and inflammation has now returned to the forefront of clinical oncology.

Contribution of Angiogenesis to Inflammation and Cancer

“…In response to these factors, the endothelial cells promote angiogenesis. The endothelial cells proliferate and migrate to form new capillaries contributing to restoring nutrient levels and facilitating immune cell migration (53).…”

“…Pro-inflammatory cytokines, such as IL-1 and IL-6, and growth factors, such as TGF-β and VEGF, then can activate various signaling pathways, primarily those involving NF-κB and STAT3 (64). It has been demonstrated that both NF-κB and STAT3 stimulate various survival signals in cells, associated with triggering the carcinogenesis process (53,65). Other soluble factors generated in the inflammatory process include VEGF-A, cyclooxygenase-2, and prostaglandins.…”

A Two‐Step Multicomponent Synthetic Approach and Anti‐inflammatory Evaluation of N‐Substituted 2‐Oxopyrazines

“…Having the collection of diversely decoratedp eptidic pyrazinones in hand, we proceeded to evaluatet he potentialo f these compounds for anti-inflammatory activity.I nflammation is ap hysiological response that, if uncontrolled, is associated with the development and progression of several illnesses, including cardiovascular disease, allergies, diabetes and metabolic syndrome, and immunologic disorders. [19] Even more, there is enough evidencet oe stablish aw ide relationship between certain kinds of cancer and inflammation, [20] as inflammatory cells are indispensable contributorst ot he neoplastic process. [21] Pyrazinones 10 a-aa were evaluated in an in vivo topi- cal anti-inflammatory model by using tetradecanoylphorbol acetate (TPA), also called phorbol-12-myristate 13-acetate (PMA), [22] as an inducer of edema.…”

Discovery of isoplumbagin as a novel NQO1 substrate and anti-cancer quinone

“…Chronic inflammation facilitates the initiation and progression of cancer [7]. Although isoplumbagin is known to exert pharmaceutical effects, no report thus far demonstrates its anti-cancer effect.…”