Chronotherapy in Glioblastoma: State of the art and future perspectives
Marina Petković,
Melad Henis,
Oliver Heese,
Angela Relógio
Affiliations
Marina Petković
Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin 10117, Germany
Melad Henis
Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg 20457, Germany
Oliver Heese
Department of Neurosurgery and Spinal Surgery, HELIOS Medical Center Schwerin, University Campus of MSH Medical School Hamburg, Hamburg 20457, Germany
Angela Relógio
Institute for Theoretical Biology (ITB), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin 10117, Germany; Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg 20457, Germany; Medical Department of Hematology, Oncology, and Tumour Immunology, Molecular Cancer Research Center (MKFZ), Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin 10117, Germany; Corresponding author.
Summary: Circadian rhythms regulate various processes in the human body, including drug metabolism. Chronotherapy optimizes treatment timing based on the circadian rhythm of the individual patient, such that the treatment efficacy is maximized, and adverse effects are minimized. It has been explored in different cancers with varying conclusions. Glioblastoma multiforme (GBM) is the most aggressive type of brain tumour with a very dismal prognosis. In recent years, there has been very little success in designing successful therapies to fight this disease. Chronotherapy offers the opportunity to leverage existing treatments to extend patient survival and to increase their quality of life. Here, we discuss recent advances in using chronotherapy regimens in the treatment of GMB, such as radiotherapy, temozolomide (TMZ) and bortezomib, as well as discuss novel treatments with drugs of short half-life or circadian phase specific activity, and examine the therapeutic potential of new approaches that target elements of the core circadian clock.
