Metabolic theory of cancer
{{Short description|A theory of cancer based on cellular metabolism}}
{{merge to|Causes of cancer|discuss=Talk:Causes of cancer#Merge Proposal|date=January 2025}}
The metabolic theory of cancer is the hypothesis that the primary cause of cancer is changes in cellular metabolism. The theory is strongly linked to the idea that diet can be used to prevent or treat many or most types of cancer.{{cite book |last1=Seyfried |first1=Thomas N. |title=Cancer as a metabolic disease: on the origin, management, and prevention of cancer |date=2012 |publisher=Wiley |location=Hoboken, N.J |isbn=978-0-470-58492-7}} It is widely accepted that changes in cellular metabolism—specifically, an increased reliance on glucose for energy, and up-regulation of anabolic processes—do occur in many types of cancer cells.{{cite journal |last1=Tufail |first1=Muhammad |last2=Jiang |first2=Can-Hua |last3=Li |first3=Ning |title=Altered metabolism in cancer: Insights into energy pathways and therapeutic targets. |journal=Molecular Cancer |date=Sep 2024 |volume=23 |issue=1 |pages=203 |doi=10.1186/s12943-024-02119-3 |doi-access=free |pmid=39294640|pmc=11409553 }} However, the idea that cancer can be controlled mostly or entirely by diet does not have broad acceptance in the medical field.
Key principles of the metabolic theory of cancer
The metabolic theory of cancer is built upon several well-known biochemical differences between normal and rapidly-proliferating cells, including:
- Warburg effect: In the 1920s, Otto Warburg observed that cancer cells prefer to generate energy through anaerobic fermentation, even when oxygen is plentiful. This is different from normal cells, which use oxygen-dependent oxidative phosphorylation for more efficient energy production.{{cite journal |last1=Warburg |first1=O |title=On the origin of cancer cells |journal=Science |date=24 Feb 1956 |volume=123 |issue=3191 |pages=309–314 |doi=10.1126/science.123.3191.309 |pmid=13298683|bibcode=1956Sci...123..309W }} As a result, cancer cells rely heavily on glucose (sugar) for energy, and produce significant amounts of lactate.{{cite journal |last1=Vander Heiden |first1=MG |last2=Cantley |first2=LC |last3=Thompson |first3=CB |title=Understanding the Warburg effect: the metabolic requirements of cell proliferation. |journal=Science |date=22 May 2009 |volume=324 |issue=5930 |pages=1029–33 |doi=10.1126/science.1160809 |pmid=19460998|pmc=2849637 |bibcode=2009Sci...324.1029V }}
- Mitochondrial dysfunction: Proponents of the metabolic theory argue that mitochondrial dysfunction plays a crucial role in cancer. Mitochondria are the cell’s energy factories and play a role in regulating cell death (apoptosis).{{cite journal |last1=Seyfried |first1=TN |last2=Flores |first2=RE |last3=Poff |first3=AM |last4=D'Agostino |first4=DP |title=Cancer as a metabolic disease: implications for novel therapeutics. |journal=Carcinogenesis |date=March 2014 |volume=35 |issue=3 |pages=515–27 |doi=10.1093/carcin/bgt480 |pmid=24343361|pmc=3941741 }} Alterations in mitochondrial morphology are evident in several types of cancer cells.
- Metabolic flexibility and glutamine dependence: Cancer cells often rely on glutamine as an alternative energy source and as a building block for growth, especially when glucose is limited.{{cite journal |last1=DeBerardinis |first1=RJ |last2=Cheng |first2=T |title=Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. |journal=Oncogene |date=21 January 2010 |volume=29 |issue=3 |pages=313–24 |doi=10.1038/onc.2009.358 |pmid=19881548|pmc=2809806 }} This metabolic flexibility allows cancer cells to adapt and thrive under varying conditions, making them more resistant to standard treatments like chemotherapy.{{cite journal |last1=Altman |first1=BJ |last2=Stine |first2=ZE |last3=Dang |first3=CV |title=From Krebs to clinic: glutamine metabolism to cancer therapy. |journal=Nature Reviews. Cancer |date=October 2016 |volume=16 |issue=10 |pages=619–34 |doi=10.1038/nrc.2016.71 |pmid=27492215|pmc=5484415 }}
Therapeutic implications and controversy
Low-carbohydrate or ketogenic diets have been suggested as an adjunct to first-line cancer therapy. These diets greatly reduce levels of glucose in body fluids, thus starving cancer cells of their preferred energy source.{{cite journal |last1=Weber |first1=DD |last2=Aminzadeh-Gohari |first2=S |last3=Tulipan |first3=J |last4=Catalano |first4=L |last5=Feichtinger |first5=RG |last6=Kofler |first6=B |title=Ketogenic diet in the treatment of cancer - Where do we stand? |journal=Molecular Metabolism |date=March 2020 |volume=33 |pages=102–121 |doi=10.1016/j.molmet.2019.06.026 |pmid=31399389|pmc=7056920 }}
However, the metabolic theory is still under investigation and remains controversial. While there is evidence supporting the role of altered metabolism in cancer, many researchers are now examining cancer as a complex interplay of genetic mutations and metabolic dysregulation, rather than a purely genetic or purely metabolic disease.{{cite journal |last1=Pavlova |first1=NN |last2=Thompson |first2=CB |title=The Emerging Hallmarks of Cancer Metabolism. |journal=Cell Metabolism |date=12 January 2016 |volume=23 |issue=1 |pages=27–47 |doi=10.1016/j.cmet.2015.12.006 |pmid=26771115|pmc=4715268 }} As of 2020, no randomized controlled trials of ketogenic diets in cancer treatment had been conducted.
See also
References
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