The Outcome of Tumor Ablation Therapies is Determined by Stress Signaling Networks

Abstract

Increasingly prominent roles in interventional oncology are held by various tumor ablation therapies performed by direct applications of local acute trauma-inducing insult to the targeted lesion aiming for its rapid in situ destruction. These therapies include treatments based on various forms of thermal energy delivery (photothermal, cryoablation, microwave ablation, radiofrequency ablation), non-thermal illumination (photodynamic therapy), electric field exposure, or high hydrostatic pressure [1-3]. Common injury inflicted in cells of tumors treated by ablation therapies is the impairment of proteostasis due to accumulation of misfolded/damaged proteins. This is sensed by afflicted cells as a trauma typically associated with thermal or oxidative stress that threatens the integrity and homeostasis at the affected site [4]. These types of stress provoke evolutionary well conserved canonic protection mechanisms based on cellular stress signaling network that serves to re-balance biochemical activities within the cell. They work by conversing the incoming signal (appearance of stressor molecule) towards downstream effector molecules involved in transcriptome reprogramming aimed at activation or inhibition of targeted biochemical tasks [4,5]. The aim of this commentary is to emphasize that the activity of the engaged intracellular signaling pathways determines the fate of involved tumor cells and ultimately the outcome of the applied therapies.