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.
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