Toxicity and efficacy of chronomodulated chemotherapy: a systematic review

Printezi, Markella I; Kilgallen, Aoife B; Bond, Marinde J G; Štibler, Urška; Putker, Marrit; Teske, Arco J.; Cramer, Maarten J.; Punt, Cornelis J.A.; Sluijter, Joost P.G.; Huitema, Alwin D. R.; May, Anne M.; Laake, Linda W. van

doi:10.1016/s1470-2045(21)00639-2

Cited by 46 publications

(40 citation statements)

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“…For example, pharmacological activation of REV-ERBs and RORs were reported to induce lethality in CRC [ 52 , 53 ] and a chrono-modulated FOLFOX treatment in metastatic CRC patients resulted in survival advantage over conventional treatment, especially in men [ 18 ]. In a recent systematic review of 18 clinical studies with 2547 cancer patients (e.g., colorectal, nasopharyngeal, endometrial and ovarian cancer) the authors concluded that chronomodulated chemotherapy resulted in reduced treatment toxicity while maintaining treatment efficacy in most cases (61% of the studies), compared with conventional therapy regimens [ 54 ]. Since MACC1 also acts as a therapeutic target restricting CRC progression and metastasis [ 24 ], a circadian MACC1 regulation is likely to affect the efficacy of treatment and would be expected to be circadian time-dependent.…”

Section: Discussionmentioning

confidence: 99%

Core-Clock Genes Regulate Proliferation and Invasion via a Reciprocal Interplay with MACC1 in Colorectal Cancer Cells

Basti

Malhan

Dumbani

et al. 2022

Cancers

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The circadian clock coordinates the timing of several cellular processes including transcription, the cell cycle, and metabolism. Disruptions in the clock machinery trigger the abnormal regulation of cancer hallmarks, impair cellular homeostasis, and stimulate tumourigenesis. Here we investigated the role of a disrupted clock by knocking out or knocking down the core-clock (CC) genes ARNTL, PER2 or NR1D1 in cancer progression (e.g., cell proliferation and invasion) using colorectal cancer (CRC) cell lines HCT116, SW480 and SW620, from different progression stages with distinct clock phenotypes, and identified mechanistic links from the clock to altered cancer-promoting cellular properties. We identified MACC1 (metastasis-associated in colon cancer 1), a known driver for metastasis and an EMT (epithelial-to-mesenchymal transition)-related gene, to be significantly differentially expressed in CC manipulated cells and analysed the effect of MACC1 manipulation (knockout or overexpression) in terms of circadian clock phenotype as well as cancer progression. Our data points to a bi-directional MACC1-circadian clock interplay in CRC, via CC genes. In particular, knocking out MACC1 reduced the period of oscillations, while its overexpression increased it. Interestingly, we found the MACC1 protein to be circadian expressed in HCT116 WT cells, which was disrupted after the knockout of CC genes, and identified a MACC1-NR1D1 protein–protein interaction. In addition, MACC1 manipulation and CC knockout altered cell invasion properties of HCT116 cells, pointing to a regulation of clock and cancer progression in CRC, possibly via the interaction of MACC1 with core-clock genes.

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Section: Discussionmentioning

confidence: 99%

Core-Clock Genes Regulate Proliferation and Invasion via a Reciprocal Interplay with MACC1 in Colorectal Cancer Cells

Basti

Malhan

Dumbani

et al. 2022

Cancers

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“…The circadian system is an emerging field in cancer therapy, as it plays an important role in drug metabolism and consequently in treatment toxicity, tolerability and efficacy of treatment [ 7 , 11 , 29 ]. However, the role of natural plant extracts upon circadian clock modulation is far from being understood.…”

Section: Discussionmentioning

confidence: 99%

“…Among these are the cell cycle/cell proliferation and metabolism [ 4 , 5 , 6 ]. Malfunctions of the circadian clock are associated with different pathologies, including cancer and studies have linked the disruption of the clock to an enhanced susceptibility to develop cancer, bad treatment response and poor prognosis [ 7 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Effects of Cynara Cardunculus in Colorectal Cancer Cells Are Modulated by the Circadian Clock

Fuhr

Basti²,

Brás³

et al. 2022

IJMS

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The circadian clock generates 24 h rhythms in behavioural, cellular and molecular processes. Malfunctions of the clock are associated with enhanced susceptibility to cancer, worse treatment response and poor prognosis. Clock-controlled genes are involved in cellular processes associated with tumour development and progression including metabolism of drugs and the cell cycle. Cynara cardunculus, a plant of the Asteraceae family, has been reported to have antiproliferative effects on breast cancer cells. Here, we used the human colorectal cancer (CRC) cell line HCT116 and its knockout variants for different core-clock genes (BMAL1, PER2, NR1D1), to investigate the treatment effect of C. cardunculus lipophilic leaf extract under different clock scenarios. Our results show a direct effect of C. cardunculus on the circadian phenotype of the cells, as indicated by alterations in the phase, amplitude, and period length of core-clock gene oscillations. Furthermore, our data indicate a role for the circadian clock in sensitivity to C. cardunculus treatment. In particular, the treatment inhibited proliferation and induced cytotoxicity and apoptosis in a clock knockout-specific manner, in CRC cells. These results point to a potential effect of C. cardunculus lipophilic leaf extracts as a modulator of the circadian clock, in addition to its anti-proliferative properties.

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“…L'administration de médicaments à un moment précis de la journée, ou chronothérapie, peut s'avérer bénéfique pour mieux traiter ces maladies, en améliorant l'efficacité des médicaments et en réduisant les effets indésirables [50]. Si la chronothérapie est encore peu considérée dans le traitement des maladies inflammatoires, cette stratégie a pourtant été utilisée avec succès dans des maladies comme les cancers, indiquant la faisabilité et la pertinence d'une telle approche [51][52][53].…”

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Récepteurs nucléaires et rythmes circadiens

Duez

Pourcet

2022

Med Sci (Paris)

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L’horloge circadienne programme l’ensemble des processus physiologiques, dont l’activité du système immunitaire, à des moments précis de la journée. Elle permet d’optimiser les fonctions de l’organisme en anticipant les changements quotidiens tels que les cycles jour/nuit. Nos habitudes de vie comme l’exposition à la lumière artificielle ou une prise alimentaire irrégulière désynchronisent cependant cette horloge et provoquent des maladies, par exemple inflammatoires. Au niveau moléculaire, elle consiste en un réseau de facteurs de transcription dont certains sont des récepteurs nucléaires, activables par des ligands. Une meilleure compréhension des rythmes biologiques et du rôle des récepteurs nucléaires de l’horloge circadienne permettrait d’ouvrir un champ thérapeutique nouveau. La chronothérapie qui consiste en l’administration d’un composé pharmacologique au moment de la journée le plus propice, permettrait, en ciblant ces récepteurs, d’optimiser l’efficacité du traitement et d’en réduire les possibles effets secondaires.

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Toxicity and efficacy of chronomodulated chemotherapy: a systematic review

Cited by 46 publications

References 50 publications

Core-Clock Genes Regulate Proliferation and Invasion via a Reciprocal Interplay with MACC1 in Colorectal Cancer Cells

Core-Clock Genes Regulate Proliferation and Invasion via a Reciprocal Interplay with MACC1 in Colorectal Cancer Cells

Antiproliferative Effects of Cynara Cardunculus in Colorectal Cancer Cells Are Modulated by the Circadian Clock

Récepteurs nucléaires et rythmes circadiens

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