RCB Foundations: Overview

The Foundations of Radiochronobiology

The Foundations of Radiochronobiology is an open-access resource that bridges radiation biology and chronobiology. The illustration shows the knowledge base for hallmark endpoints, including the number of peer-reviewed, cross-disciplinary publications as of July 2024. The studies demonstrate the molecular links between radiation effects, circadian orchestration, cellular functions, and disease phenotypes.

(c) Britta Langen, June 29, 2026.

A Quarter Century in the Making

In early January 2000, Douglas Hanahan and Robert A. Weinberg published The Hallmarks of Cancer in Cell. They proposed six features that basically all cancers were thought to acquire:

  • Self-sufficiency in growth signals
  • Insensitivity to growth-inhibitory (antigrowth) signals
  • Evasion of programmed cell death (apoptosis)
  • Limitless replicative potential
  • Sustained angiogenesis
  • Tissue invasion and metastasis.

For the first time, cancer was defined through functional capabilities on the tissue, cellular, and molecular levels. The goal was to shape cancer research into a logical science over the next quarter century where the disease would “become understandable in terms of a small number of underlying principles”.1

Eleven years later, Hanahan and Weinberg published The Next Generation and introduced the emerging hallmarks

  • Deregulating cellular energetics
  • Avoiding immune destruction

and the enabling characteristics

  • Genome instability and mutation
  • Tumor-promoting inflammation.

Surprisingly, the update did not include the disruption of the circadian clock via genetic dysregulation, although the connection between chronodisruption and cancer had been described as early as 2003 with 17 peer-reviewed publications until early 2011.3–17

In 2014, Mary-Keara Boss, Robert Bristow, and Mark W. Dewhirst linked the history of radiation biology to the hallmarks of cancer.18 Since, the Hallmarks concept has been expanded by various authors with the latest iteration by Guisheng Zhang adding the radiogenomic landscape in April 2026.21

Chronobiology has not yet been included in those efforts, illustrating how cross-disciplinary research with smaller fields can sometimes lag behind our scientific ambitions.

Now, a quarter century after Hanahan and Weinberg’s landslide publication, it is time to bridge radiation biology and chronobiology and integrate circadian rhythmicities into cellular functions and disease-defining capabilities.

The Foundations of Radiochronobiology are a stepping stone towards that goal: an open-access literature review that shows the molecular links between radiation effects, circadian orchestration, cellular functions, and disease phenotypes.

Browse the Foundations of Radiochronobiology

Dive into the science that shows how circadian rhythmicities
shape the quantity and quality of ionizing radiation-induced effects.

DNA damage
&
repair

How biological clocks influence the DDR machinery.

Explore

Radiation
metabolomics

How circadian time and
radiation change metabolic states and turnover.

Explore

Cell death
&
apoptosis

How pro vs anti survival is governed by the light-dark cycle.

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Senescence
&
quiescence

How cellular outcomes depend not only on absorbed dose, but also on time-of-day.

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Immune
modulation &
inflammation

How the molecular clock modulates the immune system.

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Cell cycle
&
survival

How the cell cycle and its disruption interconnect with the light-dark cycle.

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Bystander signaling,
ROS &
free radicals

How signaling cascades change
along 24-hour rhythms.

Explore

Radiation transcriptomics
&
proteomics

How circadian orchestration modulates radiation-induced gene regulation.

Explore

References

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. doi: 10.1016/s0092-8674(00)81683-9.
  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013.
  3. Behrens T, Mester B, Hense S, Ahrens W. Further potentially carcinogenic effects of chronodisruption. Dtsch Arztebl Int. 2011 Jan;108(1-2):8;
    author reply 8-9. doi: 10.3238/arztebl.2011.0008a.
  4. Erren TC. Shift work, cancer and “white-box” epidemiology: Association and causation. Epidemiol Perspect Innov. 2010 Nov 30;7:11.
    doi: 10.1186/1742-5573-7-11.
  5. Mester B, Behrens T, Dreger S, Hense S, Fritschi L. Occupational causes of testicular cancer in adults. Int J Occup Environ Med. 2010 Oct;1(4):160-70.
    PMID: 23022805.
  6. Erren TC, Falaturi P, Morfeld P, Knauth P, Reiter RJ, Piekarski C. Shift work and cancer: the evidence and the challenge. Dtsch Arztebl Int. 2010 Sep;107(38):657-62. doi: 10.3238/arztebl.2010.0657.
  7. Erren TC, Falaturi P, Reiter RJ. Research into the chronodisruption-cancer theory: the imperative for causal clarification and the danger of causal reductionism. Neuro Endocrinol Lett. 2010;31(1):1-3. PMID: 20150863.
  8. Reiter RJ, Tan DX, Erren TC, Fuentes-Broto L, Paredes SD. Light-mediated perturbations of circadian timing and cancer risk: a mechanistic analysis. Integr Cancer Ther. 2009 Dec;8(4):354-60. doi: 10.1177/1534735409352026.
  9. Korkmaz A, Topal T, Tan DX, Reiter RJ. Role of melatonin in metabolic regulation. Rev Endocr Metab Disord. 2009 Dec;10(4):261-70.
    doi: 10.1007/s11154-009-9117-5.
  10. Erren TC, Reiter RJ. Preventing cancers caused by chronodisruption: blocking blue light alone is unlikely to do the trick. Med Hypotheses. 2009 Dec;73(6):1077-8. doi: 10.1016/j.mehy.2009.05.003.
  11. Erren TC, Reiter RJ. Defining chronodisruption. J Pineal Res. 2009 Apr;46(3):245-7. doi: 10.1111/j.1600-079X.2009.00665.x.
  12. Erren TC, Morfeld P, Stork J, Knauth P, von Mülmann MJ, Breitstadt R, Müller U, Emmerich M, Piekarski C. Shift work, chronodisruption and cancer?–The IARC 2007 challenge for research and prevention and 10 theses from the Cologne Colloquium 2008. Scand J Work Environ Health. 2009 Jan;35(1):74-9.
    doi: 10.5271/sjweh.1303.
  13. Erren TC, Reiter RJ. A generalized theory of carcinogenesis due to chronodisruption. Neuro Endocrinol Lett. 2008 Dec;29(6):815-21.
    PMID: 19112419.
  14. Erren TC, Reiter RJ, Piekarski C. Chronodisruption and melatonin: the need for sensible exposure metrics in epidemiological studies. J Pineal Res. 2008 Oct;45(3):335-6. doi: 10.1111/j.1600-079X.2008.00599.x.
  15. Erren TC, Pape HG, Piekarski C, Reiter RJ. Not all shifts are equal: it’s time for comprehensive exposure metrics in chronodisruption research. Cancer Res. 2008 May 15;68(10):4011. doi: 10.1158/0008-5472.CAN-08-0279.
  16. Erren TC, Pape HG, Reiter RJ, Piekarski C. Chronodisruption and cancer. Naturwissenschaften. 2008 May;95(5):367-82.
    doi: 10.1007/s00114-007-0335-y.
  17. Reiter RJ, Tan DX, Korkmaz A, Erren TC, Piekarski C, Tamura H, Manchester LC. Light at night, chronodisruption, melatonin suppression, and cancer risk: a review. Crit Rev Oncog. 2007 Dec;13(4):303-28. doi: 10.1615/critrevoncog.v13.i4.30.
  18. Erren TC. Could visible light contribute to the development of leukaemia and other cancers in children? Med Hypotheses. 2005;64(4):864-71.
    doi: 10.1016/j.mehy.2004.09.021.
  19. Erren TC, Reiter RJ, Piekarski C. Light, timing of biological rhythms, and chronodisruption in man. Naturwissenschaften. 2003 Nov;90(11):485-94.
    doi: 10.1007/s00114-003-0468-6.
  20. Boss MK, Bristow R, Dewhirst MW. Linking the history of radiation biology to the hallmarks of cancer. Radiat Res. 2014 Jun;181(6):561-77.
    doi: 10.1667/RR13675.1.
  21. Zhang G, Guo Y, Yang Y, Li T, Gong B, Lou J, Li Y, Peng S, Liu C, Yuan X, Zhang F, Yang L. Radiogenomic landscape of the hallmarks of cancer. Biomark Res. 2026 Apr 21;14(1):57. doi: 10.1186/s40364-026-00920-4.