Inflammation and cancer: how friendly is the relationship for cancer patients?

Abstract

Evidence has emerged in the last two decades that at the molecular level most chronic diseases, including cancer, are caused by a dysregulated inflammatory response. The identification of transcription factors such as NF-kappaB, AP-1 and STAT3 and their gene products such as tumor necrosis factor, interleukin-1, interleukin-6, chemokines, cyclooxygenase-2, 5 lipooxygenase, matrix metalloproteases, and vascular endothelial growth factor, adhesion molecules and others have provided the molecular basis for the role of inflammation in cancer. These inflammatory pathways are activated by tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli, which together account for as much as 95% of all cancers. These pathways have been implicated in transformation, survival, proliferation, invasion, angiogenesis, metastasis, chemoresistance, and radioresistance of cancer, so much so that survival and proliferation of most types of cancer stem cells themselves appear to be dependent on the activation of these inflammatory pathways. Most of this evidence, however, is from preclinical studies. Whether these pathways have any role in prevention, progression, diagnosis, prognosis, recurrence or treatment of cancer in patients, is the topic of discussion of this review. We present evidence that inhibitors of inflammatory biomarkers may have a role in both prevention and treatment of cancer.

Fig.1

Activation of inflammatory pathway mediated through NF-κB by life-style related factors such as tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation and environmental stimuli that account for as much as 95% of all cancers. Suppression of inflammatory pathway by life style –related agents such as vegetables, fruits, legumes, grains, spices and exercise (such as Yoga), is indicated.

Fig. 2

Activation of various inflammatory pathways that lead to expression of gene products linked to cellular transformation, survival, proliferation, invasion, angiogenesis and metastasis of cancer.

Fig. 3

A model for regulation of inflammatory biomarkers. Disease is normally due to dysregulation of numerous inflammatory biomarkers (represented by each bulb). Complete inhibition of a single biomarker (such as COX2) is more likely to be toxic and unlikely to cure the disease. However, downregulation of several biomarkers partially is more likely to inhibit the dysregulated inflammation, be less toxic and more efficient in treating the disease.