Circadian system ageing in cancer: from tumourigenesis to treatment

Descripción del proyecto

El efecto del envejecimiento en la biología circadiana del cáncer

La edad es uno de los principales factores de riesgo de cáncer. El deterioro de los ritmos circadianos con el envejecimiento puede alterar la biología del cáncer y las respuestas al tratamiento. Entre las preguntas fundamentales figuran si el envejecimiento modifica el efecto de la alteración circadiana sobre los tumores y cómo influye en los ritmos tumorales ya establecidos. En el proyecto CircTu-Age, financiado por el Consejo Europeo de Investigación, se combinarán modelos avanzados del envejecimiento y el cáncer con alteraciones selectivas de los ritmos circadianos para estudiar el efecto del envejecimiento en la biología circadiana del cáncer. Esta investigación contribuirá a dilucidar la relación entre el deterioro del ritmo circadiano (una nueva característica del envejecimiento) y el cáncer, una enfermedad prevalente relacionada con la senescencia. Los resultados podrían ayudar a identificar intervenciones para reducir el riesgo de cáncer en etapas posteriores de la vida y hacer avanzar el campo de la cronoterapia del cáncer.

Objetivo

Age is cancer's primary risk factor and a significant determinant of how the resulting disease presents and
progresses. Yet the specific contribution of ageing’s diverse hallmarks to this phenomenon is poorly defined.
Circadian rhythms are a conserved adaptation that enables organisms to anticipate daily environmental
cycles and thus mitigate their harmful effects on the body. However, in recent years, a decay of homeostatic
cellular, tissue and systemic circadian rhythms has emerged as a hallmark of mammalian ageing.
Concurrently, in the context of cancer, circadian inputs from the host are known to drive daily rhythms in
tumour microenvironment composition, metastasis seeding and treatment response, whilst disruption of
physiological circadian rhythms is itself an established tumour promoter. When considered together, this
raises the intriguing possibility that ageing of the circadian system may reshape cancer circadian biology in a
manner pertinent to its prevention or treatment.

In particular, three key questions emerge: 1) Does ageing of the body and its circadian rhythm system change
the tumourigenic potency of circadian rhythm disruption? 2) Are the circadian rhythms of an established
tumour altered by ageing of the host and its circadian system? 3) If cancer circadian biology is rewired by
ageing, can we identify where this change originates from?

In CircTu-Age, we will combine cutting-edge models of ageing and cancer with targeted circadian rhythm
disruption and circadian-omics to define how ageing impinges upon the circadian biology of cancer. This
timely project will reveal the as-yet-uncharacterised interaction between an emerging hallmark of ageing,
circadian rhythm decay, and the most common of age-related diseases, cancer. The knowledge generated by
CircTu-Age will provide a roadmap for identifying interventions that diminish cancer risk later in life, and
contribute to refining and expanding the burgeoning field of cancer chronotherapy.