Targeting the Seven Cancer Hallmarks by Modulation of Oxidative Stress-induced Inflammation and Immune Activation: A Radical Therapeutic Approach

Abstract

Cancer killed approximately 8.8 million people in 2015 globally. Furthermore, more than 27,000 Kenyans die annually from cancers, making it number three killers after infectious and cardiovascular diseases. The current therapeutic strategies are limited in their approach, therefore not effective enough to achieve complete remission. A radical multifactorial approach targeting early events in carcinogenesis is required. The purpose of this descriptive study was to review existing studies for knowledge, research gaps in the role of oxidative stress, inflammation, immune activation in carcinogenesis and cancer hallmarks, to stimulate new research ideas which can accelerate future therapeutic target discoveries. PubMed, ScienceDirect and Google scholar databases were searched using the keywords: cancer, oxidative stress, inflammation, immune activation, carcinogenesis and cancer hallmarks. Although widely recognized, little research on oxidative stress, inflammation, immune activation, as cancer therapeutic targets has been done. In addition, studies relating oxidative stress, inflammation, immune activation with cancer hallmarks, especially replicative immortality, immune evasion, and evading growth suppression are inadequate. To highlight this, out of a total of 8,680,095 hits, only 139,694 hits related to oxidative stress, inflammation, immune activation as therapeutic targets making this area a fertile ground for future research. Similarly, out of 271, 194 hits, only 4,595 were relating oxidative stress, inflammation and immune activation with replicative immortality as a cancer hallmark. Subsequently, after pearling, 129 articles that were directly relevant to the study were selected. After critical appraisal, identified studies were analyzed, results compared and presented in form of summary tables. Despite enough documented evidence of the essential role oxidative stress, inflammation, immune activation, plays in carcinogenesis, specific role in induction of cancer hallmarks, whether causal or consequence is not clear. An understanding of the early changes that marks initiation, maintenance and progression of cancer will accelerate development of future novel therapeutic targets and prevention strategies. This will have a direct impact on prevention, early diagnosis, management and treatment of cancers in Africa, thereby helping in attainment of United Nations sustainable development goal (SDG) number three.