Non-stationary statistical modeling of circadian oscillations for research in cancer chronotherapy

振荡器在自然界的所有层面上都能找到。最突出的例子之一是昼夜节律，它显示出大约24小时的内生、可携带的振荡。时间疗法是一种个性化治疗形式，按照与人的节律相对应的时间表进行治疗，以最大限度地提高疗效并将治疗的副作用降至最低。目前在实验模型和患者中都有大量证据表明，患者的昼夜节律计时系统(CTS)正在影响抗癌药物的治疗耐受性和疗效，而疾病的进展和抗癌药物的治疗对CTS具有破坏性影响。我们的项目专注于开发统计方法，解决这种时变效应的建模问题。一个重要的目标是开发一种患者CTS状态的实时预测系统，以实现改进的个性化计时治疗。

Oscillators are found on all levels in Nature. One of the most prominent examples is the circadian rhythm which displays an endogenous, entrainable oscillation of about 24 hours. Chronotherapy is a form of personalized therapy where treatments are administered according to a schedule that corresponds to a person's rhythms in order to maximize effectiveness and minimize side effects of the therapy. There is now large evidence both in experimental models and in patients that the Circadian Timing System (CTS) of patients is affecting treatment tolerability and efficacy of anticancer drugs while the progression of the disease and treatment with anticancer drugs have disruptive effect on the CTS. Our projects focuses on the development of statistical methods that address the modeling of such time varying effects. An important aim is to develop a real-time prediction system of a patient's CTS state in order to achieve an improved personalized chronotherapy.