The critical role of spatio-temporal control in combinatorial chemo- and magnetic hyperthermia thermo-therapy: ‘the where’, ‘the how’ and ‘the when’

ABSTRACT Combinatorial treatments hold the key to the future of cancer treatment as they enhance therapeutic indexes by inducing synergistic effects and reducing resistance processes, while often providing a safer option for patients with fewer off-target effects. However, combinatorial treatments bring extra problems to cancer management not only derived from the actual compatibility of the treatments, but also from their hands-on administration. Operational parameters such as administration order and dosing (dose, spacing) have to be optimized in order to positively impact patient prognosis. Here we present a systematic study on the optimization and the importance of these parameters within the framework of a combinatorial chemo-/thermo-therapy. Parameters like ‘where’, ‘how’ and ‘when’ are investigated in detail. Furthermore, we delve into the underlying biochemical mechanisms driving the observed effects through transcriptome analysis.