Abstract
Purpose of Review
Fasting can be defined as stress on the cell due to nutrient deprivation which modulates metabolic regulation and influences several gene expressions. During fasting, nutrient (majorly glucose) limitation forces different organs to shift their energy sources. Ketosis starts at a faster rate in absence of glucose. The cancer cells have higher dependence on glucose for their fast cell division rate. Fasting limits the adaptability of the cancer cells and increases the therapeutic efficacy of the chemotherapeutics. The main purpose of this review is to focus on the clinical result and plausible mechanism of fasting or caloric restriction on the prevention, suppression, treatment of cancer, and chemotherapy-induced toxicity reduction.
Recent Findings
Fasting has been implicated as it promotes autophagy and plays a key role as tumor inhibitory action during fasting. In addition, transcription factor p53 also gets upregulated during fasting and regulates pro-apoptotic function in tumor cells. Also, p53 transactivates different genes for ketogenesis process. Earlier reports have suggested that prolonged fasting in some of the cancer patients is considered to be safe and more capable of minimizing chemotherapy-mediated tumor growth and toxicity.
Summary
Fasting has established a critical link between minimal level of glucose and elevated ketosis, thereby possess challenging environment for cancer cell survival. Cross talk between p53 gene and ketosis shows considerable episodes of energy metabolism pathway and upregulates the tumor suppression. The level of glucose drops during fasting stage which sensitizes the cancer cells due to energy deprivation and increases the efficacy of chemotherapeutic agents.
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Data Availability
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Abbreviations
- ATP:
-
Adenosine triphosphate
- PI3K:
-
Phosphotidyl inositol 3 kinase
- Akt:
-
Protein kinase B
- mTOR:
-
Mammalian target of rapamycin
- HIF1α:
-
Hypoxia-inducible factor 1α
- c-Myc:
-
Cellular Myc
- FIS-1:
-
Mitochondrial fission protein 1
- DRP-1:
-
Dynamin-related protein 1
- SOD:
-
Superoxide dismutase
- AMP:
-
Adenosine monophosphate
- AMPK:
-
AMP-activated protein kinase
- PTEN:
-
Phosphatase and tensin homolog
- TSC-2:
-
Tuberin
- Rev-1:
-
DNA repair protein
- Sirt-6:
-
Sirtuin 6
- Ddit-4:
-
DNA damage–inducible transcript 4
- LPIN-1:
-
Lipin-1
- Cdkn1a:
-
Cyclin-dependent kinase inhibitor 1a
- Sesn-1 and 2:
-
Sestrin 1 and 2
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Ishthiaq, I.B., Waseem, M. & Banerjee, S. Understanding the Clinical Link Between Fasting and Response to Cancer Therapy. Curr Pharmacol Rep 8, 290–299 (2022). https://doi.org/10.1007/s40495-022-00293-w
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DOI: https://doi.org/10.1007/s40495-022-00293-w