Cancer and Inflammation: Promise for Biologic Therapy

Abstract

Cancers often arise as the end stage of inflammation in adults, but not in children. As such there is a complex interplay between host immune cells during neoplastic development, with both an ability to promote cancer as well as limit or eliminate it, most often complicit with the host. In humans, defining inflammation and the presence of inflammatory cells within or surrounding the tumor is a critical aspect of modern pathology. Groups defining staging for neoplasms are strongly encouraged to assess and incorporate measures of the presence of apoptosis, autophagy, and necrosis as well as the nature and quality of the immune infiltrate. Both environmental as well as genetic factors enhance the risk of cigarette smoking, H. pylori, hepatitis B/C, human papilloma virus, solar irradiation, asbestos, pancreatitis, or other causes of chronic inflammation. Identifying suitable genetic polymorphisms in cytokines, cytokine receptors, and Toll-like receptors among other immune response genes is also seen as high value as genomic sequencing becomes less expensive. Animal models which incorporate and assess not only the genetic anlagen but also the inflammatory cells and the presence of microbial pathogen [PAMPs] and damage associated molecular pattern molecules [DAMPs] are necessary. Identifying micro-RNAs involved in regulating the response to damage or injury are seen as highly promising. Although no therapeutic strategies to prevent or treat cancers based on insights into inflammatory pathways are currently approved for the common epithelial malignancies, there remains substantial interest in agents targeting COX2 or PPARγ, ethyl pyruvate, as well as steroids and several novel agents on the horizon.

NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup

“…The severity, timing, and local character of any particular inflammatory response, initiated by tissue damage, depends on the cause, location and site of the area affected, and host's condition [8]. Inflammatory oncotaxis, a term used to describe tumor growth at a site of inflammation, is occasionally seen in persons with known or occult cancer and who have local trauma [9][10][11][12].…”

C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

“…Inflammation occurs in various types of tumor, and serves a crucial function in tumor development and distant metastasis (7)(8)(9)(10). Previous studies have indicated that inflammation is associated with the formation of the tumor microenvironment by inflammatory mediators, including vasoactive amines and cytokines (11)(12)(13).…”

Pyruvate-Dependent Changes in Neutrophil Amino- and Alpha-Keto Acid Profiles or Immunity: Which Mechanisms Are Involved?

“…With respect to a clinical therapy, but there are problems: pyruvate is relatively unstable in aqueous solution and the hunt for a possible alternative here currently led, for example, to the development of ethyl pyruvate, which is a simple aliphatic ester derived from pyruvate, but as well contributed to the invention of stable aqueous solutions containing sodium pyruvate using H + (pH 3.0 -6.0) or additional Na + (20 mM) [22] [70]- [72]. And in fact, the first results seem to be promising: treatment with pyruvate or ethyl pyruvate has shown to improve survival and/or ameliorate organ dysfunction in a wide variety of pre-clinical models or clinical trials of acute illnesses such as severe sepsis, acute pancreatitis, respiratory distress syndromes, stroke, cancer or in patients undergoing cardiac surgery [18] [35] [70]- [79]. Furthermore, the therapy using pyruvate or pyruvate-related compounds was also shown to be safe, but, nevertheless, in most studies it failed to improve outcome.…”

“…catalysed by the enzymes pyrroline-5-carboxylate synthase, ornithine aminotransferase, ornithine carbamyltransferase, or carbamylphosphate synthase) or the synthesis of •NO which is required for neutrophil activation [33] [34]. And indeed, a growing consensus exists regarding a so-called "pyruvate-glutamate-ketoglutarate-arginine-ornithine-system", which especially in leukocytes, appears to hold a key role as an "intracellular turntable for amino nitrogen metabolisation" [32] [35]. The advantages to the cell seems obvious: the possibility of a rapid transition into other essential cell substrates (i.e.…”