Cancer-on-Chip and Integrative Tumor Microenvironment Sensor Technologies for Progressing Precision Radiotherapy

Precision radiotherapy, such as targeted radioligand therapy, accentuates the precise delivery of radiation to tumor cells while limiting radiation damage to surrounding normal cells. Although recent clinical trial data has shown targeted radioligand therapy to have significant patient survival benefit, it is still unavoidable that the cancer cells will eventually adapt and develop radioresistance. Thus, the study of radiotherapy-induced changes in the tumor microenvironment (TME) is crucial for developing strategies to best overcome radioresistance. To this end, organ-on-chip (OOC) systems with integrative sensors represent cutting-edge pre-clinical models for miniaturized 3D modelling and profiling of the TME. This Review features OOC systems which have demonstrated feasibility for radiation-associated studies, as well as showcased the progress of different OOC systems for profiling core components of the TME. Furthermore, this Review discusses the knowledge gap in cancer-on-chip systems with integrative TME sensors for precision radiotherapy applications. It is anticipated that this Review can kickstart the propagation of new concepts and approaches to drive a new era of miniaturized sensors on OOC systems for precision radiotherapy. There is now significant momentum to advance precision radiotherapy by overcoming inexorable radioresistance due to tumor microenvironment (TME) changes. Organ-on-chip (OOC) systems with integrative TME sensors represent cutting-edge pre-clinical models for resolving radioresistance mechanisms stemming from the complex TME. This review highlights recent radiotherapy-related OOC systems and TME sensors, as well as the current knowledge gap for precision radiotherapy applications. image