Chronobiology of the Respiratory System

*Chronobiology - The Science of Biological Time Structure*

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**Chapter 6**

**Abstract**

*and Marie-Pascale Graas*

launched considering temporal dimension.

**Keywords:** circadian rhythms NSCLC review

**1. Introduction**

(kidney, liver) [3–5].

**1.1 Circadian timing system**

Integration of Chronobiological

Concepts for NSCLC Management

*Christian Focan, Anne-Catherine Davin, Maryam Bourhaba* 

The authors reviewed pertinent experimental and clinical data allowing to consider the interest of taking into account the temporal dimension ('circadian') for prevention and management of the majority of cancers, i.e., non-small cell lung carcinoma (NSCLC). The universal importance of circadian rhythms has been acknowledged in animal or human situations regarding carcinogenesis and cancer promotion; cell kinetics, apoptosis, molecular genetics, as well as DNA repair mechanisms, platinum resistance…; molecular targets (i.e., epidermal growth factor reception-EGFR); and all lymphoid and immunology machinery components. Also chronotolerance to all chemotherapeutic agents useful for treating human lung cancer has also been evidenced. A few randomized clinical chronotherapy trials were performed in human NSCLC. One limited trial has shown apparent chronoefficiency, while in another one, chronotolerance to 5-fluorouracil and a platinum derivative were confirmed. The limited improvement of outcome in human NSCLC, even through the use of targeted and biological therapies (such as tyrosine-kinase (TKI) or vascular-endothelialgrowth-factor (VEGFR) inhibitors; immunotherapy), allows to consider launching specific trials in human NSCLC aiming at either restoring a normal circadian structure of the host or taking into account circadian variations of specific targets. By now unfortunately, no targeted or immunotherapy trials have been

Life is structured in space but also in time. Biological rhythms have been documented in all processes involved in the malignant transformation of cells as well as in the cellular proliferation of both healthy and tumor tissues [1–5]. All physiological functions expressed their metabolic or specific activities according to a circadian variation [1–5]. This is the case not only for actively dividing tissues but also for all other tissues, such as the myocardium, central nervous system, or organs involved in the metabolization, detoxification and excretion of drugs
