Targeting Inflammation in Cancer Prevention and Therapy

Abstract

Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and cancer therapy. Tumor extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. By contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immune suppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common non-steroidal anti-inflammatory drugs (NSAIDs) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches based on tumor resection, radiation and cytotoxic chemicals.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…Low-grade chronic inflammation is a primary contributor to the onset and progression of chronic kidney disease 11,142,209,210 . Inflammation is a causal factor for cancer initiation, promotion, malignancy, and metastatic dissemination 211,212 . Depression is characterized by increased levels of pro-inflammatory cytokines and acute phase proteins in both peripheral blood and cerebrospinal fluid 213,214 .…”

“…The collective evidence suggests that chronic inflammation is a risk factor across multiple diseases, some of which are traditionally viewed as pathophysiologically unrelated, such as CVD 157,159,160,220 , diabetes 138,180,221 , chronic kidney disease 11,142,209 , cancer 211,212,222 , depression 13,143,217 , and dementia 12,139,223 . In addition, higher levels of inflammatory markers in blood are associated with a greater loss of muscle mass and strength, accelerated loss of mobility, lower-extremity performance and physical activity, and depression in older individuals 224–228 , all of which are essential elements for defining frailty on the basis of the criteria most often used in the literature 229 .…”

Sildenafil Suppresses Inflammation-Driven Colorectal Cancer in Mice

“…This association provides rationale for the utility of anti-inflammatory therapies for CRC prevention (3). Indeed, epidemiological evidence has shown that long-term non-steroidal anti-inflammatory drug (NSAID) use correlates with reduced incidence of CRC including in patients without IBD (4,5).…”

Basal Cell Carcinoma Developed on an Active Lesion of Mucocutaneous Leishmaniasis: A Case Report from Yemen

“…In contrast, cancer-intrinsic inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development [6,7].…”