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Review Article


Chronomodulation of cyclin-dependent kinases 4/6 inhibitor may reduce hematological toxicities? A review of literature

Mukul Arvind Gharote
ukta Cancer Clinic, Bunglow No.61, Teerthroop Bunglow, Sundarban Colony, Near Deccan Petrol Pump, Nashik – 422009, Maharashtra, India
Corresponding Author:

Mukul Arvind Gharote

Mukta Cancer Clinic, Bunglow No.61, Teerthroop Bunglow, Sundarban Colony, Near Deccan Petrol Pump, Nashik – 422009, Maharashtra, India
E-mail: Mukul.gharote@gmail.com

Corresponding Author:

Mukul Arvind Gharote

Mukta Cancer Clinic, Bunglow No.61, Teerthroop Bunglow, Sundarban Colony, Near Deccan Petrol Pump, Nashik – 422009, Maharashtra, India
E-mail: Mukul.gharote@gmail.com

DOI:10.18203/issn.2456-3994.IntJMolImmunoOncol20184342

ABSTRACT


Nucleotide excision repair, DNA damage checkpoints, and apoptosis are under the influence of the circadian rhythm1. Circadian rhythm is defined as oscillations in the behavior and biochemical changes in an individual that repeats itself after the span of 24 h approximately. Cyclin-dependent kinase (CDK) inhibition causes cell cycle arrest and subsequent circadian stage-dependent gating of cells at G2-M interface of the cell cycle. Few anecdotes have suggested that chronomodulation reduces hematological toxicity in cell cycle-specific chemotherapy, especially S1-specific chemotherapy. In a study conducted by Boucher et al., 2016, circadian rhythm plays a role in the regulation of human mesenchymal stem cells (hMSCs) differentiation and division and likely represents key factor in maintaining hMSCs properties. If we apply the knowledge of circadian clock, then we know the fact that bone marrow stem cells (BMSCs) are under the control of circadian rhythm and G1-S phase of cell division cycle occurs at the early morning period of solar day. If CDK4/6 plasma peak level coincides with G1-S phase of BMSCs, then theoretically cytopenia may occur, which again is the sign of CDK4/6 action but is also the reason of its toxicity. Chronomodulation studies of CDK4/6 inhibitor may reduce hematological toxicity of CDK4/6 inhibitor.
Keywords: Chronomodulation, Hematological toxicity, Circadian rhythm, CDK4/6 inhibitors

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