Potential Utilization of Bystander / Abscopal-Mediated Signal Transduction Events in the Treatment of Solid Tumors

Abstract

A transformed cell among a group of normal cells exerts a dynamic influence for clonal growth and mass transformation. Likewise, a treatment-induced damaged cell might exert deleterious signal to either neighboring or distal cells. These signals that elicit either transformation or cell death are classified under two independent phenomena. These two phenomena are called (1) Abscopal effect and (2) Bystander effect. There are several agents that have been reported to induce abscopal and bystander effects. Ionizing radiation and ultraviolet radiation are prime inducers of abscopal and bystander effects. In addition, localized therapies for tumor control such as gene therapy approaches, prodrug conversion based chemotherapy approaches, and surgical procedures are significant inducers of either abscopal or bystander effects. The proposed mechanisms that have been reported in literature clearly indicate pivotal roles of cytokine and ceramide signaling leading to the activation of pro-survival proteins and/or pro-apoptotic proteins. Together these pathways provide distinct differences between abscopal and bystander effects that are of particular interest in modern cancer therapeutics. The most exciting future direction of bystander/ abscopal biology in terms of cancer therapeutics will potentially arise from the use of stem cells. In this review, a critical evaluation of potential benefits of abscopal / bystander effects mediated signaling pathways in relation to cancer therapeutics are discussed in detail.