Targeting cancer-promoting inflammation — have anti-inflammatory therapies come of age?

Abstract

The immune system has crucial roles in cancer development and treatment. Whereas adaptive immunity can prevent or constrain cancer through immunosurveillance, innate immunity and inflammation often promote tumorigenesis and malignant progression of nascent cancer. The past decade has witnessed the translation of knowledge derived from preclinical studies of antitumour immunity into clinically effective, approved immunotherapies for cancer. By contrast, the successful implementation of treatments that target cancer-associated inflammation is still awaited. Anti-inflammatory agents have the potential to not only prevent or delay cancer onset but also to improve the efficacy of conventional therapeutics and next-generation immunotherapies. Herein, we review the current clinical advances and experimental findings supporting the utility of an anti-inflammatory approach to the treatment of solid malignancies. Gaining a better mechanistic understanding of the mode of action of anti-inflammatory agents and designing more effective treatment combinations would advance the clinical application of this therapeutic approach. Chronic inflammation can promote the development of various cancers. In this Review, the current clinical advances in ameliorating inflammation for the prevention or treatment of cancer are highlighted, and the experimental insights into the biological mechanisms supporting current and potential novel anti-inflammatory approaches to the management of cancer are discussed. Inflammation-related biological processes influence all stages of cancer development and treatment; environmental risk factors and both tumour-extrinsic and tumour-intrinsic inflammatory processes have been linked to tumour initiation, promotion and progression. Several conventional drugs with anti-inflammatory properties have demonstrated protective effects against cancer but are yet to be deployed in at-risk populations and properly evaluated for therapeutic applicability. Cytokine-specific agents with anti-inflammatory activities have antitumour efficacy in preclinical studies but evidence demonstrating activity against solid tumours in clinical trials is scarce. Preclinical studies have revealed that anti-inflammatory drugs can suppress cancer development through multiple mechanisms. Monotherapy with anti-inflammatory agents can elicit cell adaptability and/or affect tumour evolution in heterogeneous cancer types, leading to therapy resistance or even accelerated disease progression. Overcoming current obstacles to the clinical introduction of anti-inflammatory therapy will require the development of effective combination regimens and the identification of reliable response biomarkers. Inflammation-related biological processes influence all stages of cancer development and treatment; environmental risk factors and both tumour-extrinsic and tumour-intrinsic inflammatory processes have been linked to tumour initiation, promotion and progression. Several conventional drugs with anti-inflammatory properties have demonstrated protective effects against cancer but are yet to be deployed in at-risk populations and properly evaluated for therapeutic applicability. Cytokine-specific agents with anti-inflammatory activities have antitumour efficacy in preclinical studies but evidence demonstrating activity against solid tumours in clinical trials is scarce. Preclinical studies have revealed that anti-inflammatory drugs can suppress cancer development through multiple mechanisms. Monotherapy with anti-inflammatory agents can elicit cell adaptability and/or affect tumour evolution in heterogeneous cancer types, leading to therapy resistance or even accelerated disease progression. Overcoming current obstacles to the clinical introduction of anti-inflammatory therapy will require the development of effective combination regimens and the identification of reliable response biomarkers.