17 May 2020: How cancer arises from chronic inflammation, based on complexity theory

I will present a paper entitled "How cancer arises from chronic inflammation, based on complexity theory", at the American Association for Cancer Research (AACR) Virtual Annual Meeting II, June 22-24, 2020. I am happy to answer questions about this paper or to hear your cancer stories. However, I cannot provide medical advice to you - instead, I suggest you contact your local medical center or medical school.

Abstract: https://www.abstractsonline.com/pp8/#!/9045/presentation/3692 and below

Abstract (PDF): http://www.natpernick.com/AACRAbstractChronicInflammationJune2020.pdf

Poster (PDF): http://www.natpernick.com/AACR2ChronicInflammation.pdf

Paper (PDF): http://www.natpernick.com/ChronicInflammationpaperMay2020.pdf

Abstract:

How cancer arises from chronic inflammation, based on complexity theory

Last revised 17 May 2020

Introduction: This paper discusses how cancer arises from chronic inflammation, based on complexity theory. We believe that this perspective may lead to new insights into cancer pathophysiology and treatment.

Methods: We reviewed the medical literature to identify cancer types strongly associated with chronic inflammation. We then classified the chronic inflammatory etiologies, determined general mechanisms through which they promote cancer and speculated on network changes involved in transforming cells from physiologic to cancer attractor states.

Results: Bacterial and viral infection, predominantly Helicobacter pylori, human papillomavirus and hepatitis B and C virus, are a common etiology of chronic inflammation associated cancer and cause 15% of cancer cases worldwide. Other etiologies are parasitic infestations by Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium; autoimmunity in Hashimoto thyroiditis, Sjögren syndrome and celiac disease; local trauma due to gastroesophageal reflux and hot beverages; excess weight; diabetes; Western diet (high fat, low fiber, low consumption of fruit and vegetables); aging and immune system dysfunction. General mechanisms through which these etiologies cause cancer are immune system activation that damages DNA by producing reactive oxygen and nitrogen species and nitrosamines; tumor immune evasion via immune suppression and immune senescence; antigen driven lymphoproliferation; continuous mitotic activity due to repair; synergy with other chronic stressors; creation of a tumor nurturing microenvironment; development of a “runaway” immune system; and microbiome changes that produce carcinogens or activate inflammation. Immune system dysfunction and germ line variations of inflammatory mediators can promote each step. From a network perspective, the usual physiologic state for many cellular processes consists of a delicate balance between stimulating and dampening forces, maintained by inherent network features and evolved control systems. Chronic inflammation may disturb this balance, leading to propagation of network instability throughout the cell, across adjacent tissues and ultimately systemically. This may create identifiable network hierarchies and intermediate states (hyperplasia, metaplasia or dysplasia), but some changes in network and molecular patterns may not alter histology. Ultimately, cells may move to a cancer attractor state.

Summary: Chronic inflammation causes cancer by initiating local changes to cellular networks and their microenvironment which facilitate their escape from physiologic states towards intermediate and cancer attractor states. This suggests that early detection and reduction of these inflammatory changes may reduce cancer mortality. Novel treatment options include more diverse treatment combinations, destabilizing existing cancer attractors and their microenvironment, stimulating physiologic pathways that steady networks, reducing other chronic stressors and optimizing rational medical care.

This manuscript has not received any outside funding. There are no known conflicts of interest.

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