Inflammation and Cancer – a primer

Dr. Weeks’  Comment: Over the past few years, I have predicted that the era of oncologists offering  the unholy trinity of “cut burn poison” (i.e. surgery, radiation and chemotherapy)  is about to end.  Why?  Because scientific research by such brilliant researchers  as Professor Max Wicha, M.D.  at U. Michigan  and Max Diehn, M.D. PhD  at Stanford  (and many others!) are ushering in the era of “centisble”  Corrective Cancer Care and the drug of choice is a humble anti-inflammatory agent: aspirin and other NSAIDs  as well as natural herbal anti-inflammatory plants such as black cumin seed, black raspberry seed and Chardonnay grape seed which compose the amazing 3 seed drink:  SOUL.  




Inflammation and Cancer

Lisa M. Coussens*†§ and Zena Werb‡§

LINK to read the entire article (well worth it!)



Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

The functional relationship between inflammation and cancer is not new. In 1863, Virchow hypothesized that the origin of cancer was at sites of chronic inflammation, in part based on his hypothesis that some classes of irritants, together with the tissue injury and ensuing inflammation they cause, enhance cell proliferation1. Although it is now clear that proliferation of cells alone does not cause cancer, sustained cell proliferation in an environment rich in inflammatory cells, growth factors, activated stroma, and DNA-damage-promoting agents, certainly potentiates and/or promotes neoplastic risk. During tissue injury associated with wounding, cell proliferation is enhanced while the tissue regenerates; proliferation and inflammation subside after the assaulting agent is removed or the repair completed. In contrast, proliferating cells that sustain DNA damage and/or mutagenic assault (for example, initiated cells) continue to proliferate in microenvironments rich in inflammatory cells and growth/survival factors that support their growth. In a sense, tumours act as wounds that fail to heal2.

Today, the causal relationship between inflammation, innate immunity and cancer is more widely accepted; however, many of the molecular and cellular mechanisms mediating this relationship remain unresolved — these are the focus of this review. Furthermore, tumour cells may usurp key mechanisms by which inflammation interfaces with cancers, to further their colonization of the host. Although the acquired immune response to cancer is intimately related to the inflammatory response, this topic is beyond the scope of this article, but readers are referred to several excellent reviews 3,4.

An overview of inflammation

To understand the role of inflammation in the evolution of cancer, it is important to understand what inflammation is and how it contributes to physiological and pathological processes such as wound healing and infection (Fig. 1). In response to tissue injury, a multifactorial network of chemical signals initiate and maintain a host response designed to ‘heal’ the afflicted tissue. This involves activation and directed migration of leukocytes (neutrophils, monocytes and eosinophils) from the venous system to sites of damage (Box 1), and tissue mast cells also have a significant role. For neutrophils, a four-step mechanism is believed to coordinate recruitment of these inflammatory cells to sites of tissue injury and to the provisional extracellular matrix (ECM) that forms a scaffolding upon which fibroblast and endothelial cells proliferate and migrate, thus providing a nidus for reconstitution of the normal microenvironment5. These steps involve: activation of members of the selectin family of adhesion molecules (L- P-, and E-selectin) that facilitate rolling along the vascular endothelium; triggering of signals that activate and upregulate leukocyte integrins mediated by cytokines and leukocyte-activating molecules; immobilization of neutrophils on the surface of the vascular endothelium by means of tight adhesion through α4β1 and α4β7 integrins binding to endothelial vascular cell-adhesion molecule-1 (VCAM-1) and MadCAM-1, respectively; and transmigration through the endothelium to sites of injury, presumably facilitated by extracellular proteases, such as matrix metalloproteinases (MMPs)….


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