Circadian disruption in lung cancer

ABSTRACT

Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the predominant cause of cancer-related mortality globally, with over a million deaths each year. This highlights the urgent need to develop a deeper understanding of the current state of cancer care. At the environmental and cellular levels, circadian rhythms are closely associated with living organisms. In humans, the suprachiasmatic nucleus is the principal circadian pacemaker. Circadian gene feedback loops regulate the clock, connecting peripheral tissue metabolism, cell proliferation, DNA repair, and cell death to energy homeostasis, physical activity, and neurohormonal regulation at the organismal level. Endogenous circadian homeostasis has been frequently disturbed in modern civilizations, resulting in a higher risk of many disorders, including lung cancer. Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the predominant cause of cancer-related mortality globally, with over a million deaths each year. This highlights the urgent need to develop a deeper understanding of the current state of cancer care. At the environmental and cellular levels, circadian rhythms are closely associated with living organisms. In humans, the suprachiasmatic nucleus is the principal circadian pacemaker. Circadian gene feedback loops regulate the clock, connecting peripheral tissue metabolism, cell proliferation, DNA repair, and cell death to energy homeostasis, physical activity, and neurohormonal regulation at the organismal level. Endogenous circadian homeostasis has been frequently disturbed in modern civilizations, resulting in a higher risk of many disorders, including lung cancer. The mammalian circadian clock controls metabolism and cell division, and disruption of these processes may lead to cancer pathogenesis. Furthermore, circadian disturbance has recently been identified as a self-regulating cancer risk factor and is listed as a carcinogen. The theory that both somatic and systemic disturbances of circadian rhythms are related to a higher risk of lung cancer development and poor prognosis is addressed in this study. The chronotherapy principles hold much more promise for enhancing the lung cancer care options currently available. Developing a better understanding of the molecular interactions that control the physiological equilibrium between both the circadian rhythm and the cycle of cell division could significantly influence the development of novel treatments for lung cancer and other diseases.

KEYWORDS:

• Lung cancer
• circadian rhythm
• chronobiology
• circadian disruption
• chronotherapeutics

Acknowledgements

We are thankful to all members of the Genomics and Systems Biology lab, Department of Zoology, The Maharaja Sayajirao University of Baroda, Gujarat, India, for their invaluable assistance. The DST-INSPIRE Fellowship (IF190507) from the Department of Science and Technology, New Delhi, India, to N.N. provided funding for this research.

Additional information

Funding

This work was supported by Department of Science and Technology, Ministry of Science and Technology, New Delhi, India [DST/INSPIRE Fellowship/IF190507.