The impact of drug holiday on drug resistance

Drug resistance greatly limits the impact of chemotherapy and targeted therapy: often, the tumor response is profound, yet transient. Whereas drug resistance can be a stably inheritable trait, evidence is accumulating that relapsed cancer patients can show a clinical response when re-challenged with the same therapy after a so-called drug holiday. This may create a promising therapeutic opportunity.

Dr. Maarten Altelaar (UIPS) and dr. Daniel Peeper (NKI) have received a KWF grant to increase our understanding of the mechanistic basis, dynamics and identity of the signaling pathways that determine the (lack of) tumor response to drug holiday. To date, there is only limited insight into the mechanism of drug holiday sensitivity. Therefore, the mechanistic basis of this phenomenon is largely unknown. It likely involves key signaling networks that are used by tumor cells to adapt to the drugs they are exposed to, which creates a selective pressure for survival and proliferation. Dissection of these processes will shed important light on the dynamics and critical players of therapy response. This type of knowledge is vital to understand which elements in cancer cells may be amenable for therapeutic intervention.