AUG 07, 2018 08:15 AM PDT

Is There a Best Time of Day to Administer Chemo?

A recent publication in the Journal of Pharmacological Sciences outlines how the efficacy of L-asparaginase is dose schedule dependent in breast-tumor bearing mice.

Asparagine is an amino acid involved in metabolic control of cell functionality in primarily nerve and brain tissue.  It is a common, non-essential amino acid synthesized by the body from oxaloacetate, which is an intermediate of the citric acid cycle in aerobic glycolysis (ATP producing pathway).  L-asparaginase is an enzyme that enhances the conversion of asparagine which is used by new cells for growth and energy for proliferation.  Without asparagine, DNA and RNA synthesis cease which results in programmed cell death.  Young, undifferentiated lymph cells (lymphoblasts) in particular are dependent on asparagine for energy.   L-asparaginase has been used for nearly a decade in patients with acute lymphoblastic leukemia (ALL) with significant success as a multi-drug chemotherapy treatment.  Researchers have been looking at its use for solid tumors in vitro but have not translated results to in vivo studies for tumor bearing patients. 

A group of Japanese researchers sought to further the understanding of L-asparaginase as a chemotherapy agent for solid tumors through investigation of its mechanism and potential efficacy dependence on changing physiological levels of asparagine in plasma.  In animals, asparagine levels in plasma vary; they are higher in the light phase of a day and much lower in the dark phase of a day. 

They specifically looked at breast-tumor cells and the anti-tumor effects of L-asparaginase in mice while varying the administration schedule to track effect.  The group maintained the mice in standardized light/dark cycle conditions to mimic days and nights.  Tumor cell growth in these mice was significantly inhibited by L-asparaginase when administered during the light cycle hours; conversely, when L-asparaginase was administered in the dark phase, there was no significant anti-tumor activity.  The evidence very clearly suggests differences in anti-tumor therapeutic efficacy of L-asparaginase in these tumorigenic mice based on when doses were given. 

It is not clear if dose schedule is considered for many chemotherapeutic agents in a clinical setting, nor if there is other research showing the value of investigating such concepts.  It is noteworthy to consider if a cancer driving mechanism has any circadian rhythm or regular pattern with potential to affect therapy outcomes.

Sources: Journal of Pharmacological Sciences, NIH PubChem, Polish Archives of Internal Medicine,

About the Author
  • Mauri S. Brueggeman is a Medical Laboratory Scientist and Educator with a background in Cytogenetics and a Masters in Education from the University of Minnesota. She has worked in the clinical laboratory, taught at the University of Minnesota, and been in post secondary healthcare education administration. She is passionate about advances and leadership in science, medicine, and education.
You May Also Like
OCT 21, 2019
Cancer
OCT 21, 2019
Can soda give me cancer?
We all know that excess consumption of sugary drinks like soda and 100% fruit juices are not good for us. The high quantities of sugar in these beverages h...
OCT 21, 2019
Cardiology
OCT 21, 2019
Childhood Cancer Survivors Prone to Cardiac Events
A new study published in the American Heart Association's journal Circulation explores the relationship between childhood cancer, metabolic conditions ...
OCT 21, 2019
Cancer
OCT 21, 2019
Can eating mushrooms reduce the risk of prostate cancer?
Now here’s a question: have you eaten your mushrooms yet today? Although mushrooms may not be one of the typically-touted snacks in the healthcare wo...
OCT 21, 2019
Drug Discovery & Development
OCT 21, 2019
Promising Drug for Prostate Cancer
Using high-throughput screening methods, cancer researchers from the UK have identified some promising drug candidates to test thousands of molecules. Spec...
OCT 21, 2019
Cancer
OCT 21, 2019
It's not all bad: cancer and aging
Research published recently in the journal Aging Cell highlights the complexities of the interactions that occur during the aging process from the angle of...
OCT 21, 2019
Cancer
OCT 21, 2019
New hope for mesothelioma treatment
Mesothelioma is a very rare kind of malignant tumor that is caused by inhaled asbestos fibers and forms in the lining of the lungs, abdomen or heart. While...
Loading Comments...