The circadian clock and cell cycle: interconnected biological circuits

Masri, Selma; Cervantes, Marlene; Sassone–Corsi, Paolo

doi:10.1016/j.ceb.2013.07.013

Cited by 106 publications

(106 citation statements)

References 48 publications

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“…En humanos, la fase S de la mucosa gastrointestinal, la piel y la médula ósea corresponde al medio día (18) o a las horas de la tarde (23)(24)(25). Independientemente de la hora de mayor replicación del ADN, el ciclo celular está fuertemente influenciado por los ritmos circadianos y tiene una duración de 24 horas (19,26).…”

Section: Regulación Del Ciclo Celular Por El Reloj Biológico Endógenounclassified

Los ritmos circadianos en cáncer y la cronoterapia

Molina-Rodríguez¹,

Álvarez²

2016

iatreia

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RESUMENLos ritmos circadianos, períodos fisiológicos de 24 horas aproximadamente, coordinan la actividad temporal de la mayoría, si no, de todos los seres vivos del planeta. Uno de los procesos más importantes del cuerpo, la proliferación celular, también está regulado por el reloj biológico cuya alteración puede tener repercusiones directas en el desarrollo del cáncer. El concepto de cronoterapia ha surgido a partir de la evidencia que tanto la proliferación de las células, como los mecanismos responsables de la farmacocinética y la farmacodinamia de los antineoplásicos ocurren a horas específicas del día. En esta revisión se presentan las generalidades del ciclo circadiano y su relación con el ciclo celular y el cáncer. Además, se expone evidencia del uso de la cronoterapia en pacientes con leucemia linfocítica aguda y en estudios clínicos de cáncer de colon, endometrio y ovario con asignación aleatoria. Se concluye que la hora de administración de la quimioterapia debe tener en cuenta los ritmos circadianos de los pacientes. Se enfatiza en la necesidad de hacer estudios clínicos enfocados en la quimioterapia cronomodulada, con el fin de aumentar la tolerancia y efectividad de los medicamentos con los protocolos existentes.

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Section: Regulación Del Ciclo Celular Por El Reloj Biológico Endógenounclassified

Los ritmos circadianos en cáncer y la cronoterapia

Molina-Rodríguez¹,

Álvarez²

2016

iatreia

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“…Indeed, host circadian rhythms have often been found to be disrupted in cancer patients and mouse cancer models [10,12,15,17]. For example, in mice with lung adenocarcinoma, circadian gene expression was largely affected in the liver, with many genes losing rhythmicity, others becoming rhythmic, and some being shifted earlier or later [15]. In humans, alterations in clock gene expression and consequently clock-controlled gene expression was documented in the healthy gut tissues surrounding the tumor [18,19].…”

Section: Targeting the Clock In Tumors?mentioning

confidence: 99%

“…In contrast to healthy cells with a cell-division rate of about 24 h, cancer cells are characterized by uncontrolled fast cell division. In fact, the literature reports that cell-cycle gene expression is altered in cancer cells [11,15] and that increased levels of the proto-oncogene Myc, upon mutation of clock genes in tumor cells, correlate with the cell-division speed [9]. Since the cell cycle is under circadian control, cancer cells might enhance their proliferation through manipulation of the circadian control over the cell cycle.…”

Section: Targeting the Clock In Tumors?mentioning

confidence: 99%

“…This is a question worth asking, given the circadian regulation of physiological systems relevant to cancer (e.g., immune responses, cell cycle, DNA repair), and the effects of circadian disruption on tumorigenesis (see the first two sections). Indeed, host circadian rhythms have often been found to be disrupted in cancer patients and mouse cancer models [10,12,15,17]. For example, in mice with lung adenocarcinoma, circadian gene expression was largely affected in the liver, with many genes losing rhythmicity, others becoming rhythmic, and some being shifted earlier or later [15].…”

Section: Targeting the Clock In Tumors?mentioning

confidence: 99%

“…Targeting the circadian clock may be a powerful tool to control tumorigenesis, since the literature reports that many cancer-related cellular processes, such as the cell cycle, cell proliferation, apoptosis and DNA damage are controlled by the circadian clock [15]. Interestingly, the targets of about half of the drugs currently on the market are encoded by genes showing circadian regulation [2].…”

Section: Considering Circadian Rhythms In Treatmentsmentioning

confidence: 99%

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The tumor circadian clock: a new target for cancer therapy?

Kiessling

Cermakian

2017

Future Oncol.

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Cancer is among the most frequent causes of death in humans. To date, established cancer therapies include surgery, radiation, chemo-and immunotherapy as well as hormonal treatments up to stem cell transplantation. In this editorial, we highlight an additional and so far underestimated factor involved in carcinogenesis and prognosis, namely biological clocks, which should be carefully considered to establish future cancer therapies. Disruption of the circadian clock was documented both in host-tissue and in cancer cells, and functional oscillations were associated with cancer prognosis and survival. We summarize recent advances in the field of chronobiology regarding the role of the host's and tumor-intrinsic circadian clock functions in carcinogenesis.The biological circadian clock controls cancer-related pathways A central clock in the hypothalamus and peripheral clocks in almost all organs and tissues altogether regulate physiological processes in a time of day dependent (circadian) manner. The molecular bases of circadian clocks are cellular oscillations generated by a number of rhythmically expressed interconnected clock genes [1]. Highthroughput experiments on murine tissues showed that in any given cell-type or organ, hundreds or thousands of genes are expressed with a circadian rhythm, and led to the estimation that around 50% of all genes oscillate in at least one organ [2]. As a consequence of this, most cellular and physiological processes show 24 h oscillations. This is the case of many aspects of the immune system, including many immune cells and responses of relevance to cancer [3]. Also, major regulators of the cell cycle and tumor suppressor genes were shown to be regulated by the circadian clock, such as WEE1, c-MYC and p21 [4]. Consistently, cell-cycle progression and proliferation show circadian regulation. Circadian clock disruption is associated with cancerMismatch between the internal clock and the external time disrupts the circadian network, as reported for example in shift workers [5], and has been associated with a wide range of pathologies and disease states including cancer [4]. Mounting evidence from human-based epidemiological studies suggested an effect of circadian disruption during shift work on cancer risk. For example, the risk to develop breast cancer was extensively increased in nurses exposed to long-term rotating night shift work [6]. Similar results were obtained for prostate cancer risk in night shift workers [7]. Out of note, in 2007 an agency of the WHO has classified night shift work leading to circadian disruption as 'probably carcinogenic' to humans [8]. Since then, there has been growing interest in understanding how circadian disruption may play a role in cancer development and progression. In support of human studies, experimental work in rodents documented accelerated tumor growth when mice, engrafted with lung adenocarcinoma or Glasgow osteosarcoma, were exposed to repeated jet lag conditions [9,10]. Similarly, enhanced tumor development has been described in mi...

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Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC

Tang

Xie

et al. 2019

Advanced Science

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Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can potentiate the cytotoxicity of oxaliplatin and boost cell apoptosis by inhibiting DNA adducts repair in human oral squamous cell carcinoma (OSCC) cells. The circadian timing system is closely involved in controling the activity of DNA adducts repair and gives it a 24 h rhythm. The mechanistic dissection clarifies that PER2 can periodically suppress proliferating cell nuclear antigen (PCNA) transcription by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Similarly, PER2 is capable of improving the efficacy of classical DNA‐damaging chemotherapeutic agents. The tumor‐bearing mouse model displays PER2 can be deployed as an oxaliplatin administration timing biomarker. In summary, it is believed that the chronochemotherapeutic strategy matching PER2 expression rhythm can efficiently improve the oxaliplatin efficacy of OSCC.

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The circadian clock and cell cycle: interconnected biological circuits

Cited by 106 publications

References 48 publications

Los ritmos circadianos en cáncer y la cronoterapia

Los ritmos circadianos en cáncer y la cronoterapia

The tumor circadian clock: a new target for cancer therapy?

Periodic Oxaliplatin Administration in Synergy with PER2‐Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC

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