Metabolic theory of cancer explained

The metabolic theory of cancer suggests that cancer is primarily a metabolic disease, meaning it arises from changes in cellular metabolism rather than solely from genetic mutations, which is the basis of the traditional genetic theory of cancer. This theory is grounded in the observation that cancer cells have unique metabolic needs and behaviors, especially related to how they produce energy.

Key principles of the metabolic theory of cancer

Warburg effect

In the 1920s, Otto Warburg observed that cancer cells prefer to generate energy through anaerobic fermentation, a process of breaking down glucose into lactate, even when oxygen is plentiful. This is different from normal cells, which use oxidative phosphorylation in the presence of oxygen for more efficient energy production.[1]

The Warburg effect indicates that cancer cells rely heavily on glucose (sugar) for energy, which has implications for dietary and therapeutic approaches.[2]

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).[3] When mitochondria are damaged or function abnormally, cells may not undergo proper apoptosis, leading to uncontrolled cell growth.[4]

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.[5] This metabolic flexibility allows cancer cells to adapt and thrive in diverse environments, making them more resistant to standard treatments like chemotherapy.[6]

Therapeutic implications

Dietary approaches: Low-carbohydrate or ketogenic diets are suggested as potentially helpful because they limit glucose availability to cancer cells, thereby "starving" them. These diets force the body to produce ketones, which cancer cells cannot easily use. Targeting metabolism in treatment: Drugs that disrupt cancer cells' metabolic processes, particularly those targeting glucose or glutamine metabolism, are being explored as cancer treatments.[7]

Controversy and research

The metabolic theory is still under investigation and remains controversial. While there is evidence supporting the role of altered metabolism in cancer, the genetic mutation model also has significant support. 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.[8] [9]

See also

Notes and References

  1. Warburg . O . On the origin of cancer cells . Science . 24 Feb 1956 . 123 . 3191 . 309–314 . 10.1126/science.123.3191.309 . 13298683. 1956Sci...123..309W .
  2. Vander Heiden . MG . Cantley . LC . Thompson . CB . Understanding the Warburg effect: the metabolic requirements of cell proliferation. . Science . 22 May 2009 . 324 . 5930 . 1029–33 . 10.1126/science.1160809 . 19460998. 2849637 . 2009Sci...324.1029V .
  3. Seyfried . TN . Flores . RE . Poff . AM . D'Agostino . DP . Cancer as a metabolic disease: implications for novel therapeutics. . Carcinogenesis . March 2014 . 35 . 3 . 515–27 . 10.1093/carcin/bgt480 . 24343361. 3941741 .
  4. Wallace . DC . Mitochondria and cancer. . Nature Reviews. Cancer . October 2012 . 12 . 10 . 685–98 . 10.1038/nrc3365 . 23001348. 4371788 .
  5. DeBerardinis . RJ . Cheng . T . Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. . Oncogene . 21 January 2010 . 29 . 3 . 313–24 . 10.1038/onc.2009.358 . 19881548. 2809806 .
  6. Altman . BJ . Stine . ZE . Dang . CV . From Krebs to clinic: glutamine metabolism to cancer therapy. . Nature Reviews. Cancer . October 2016 . 16 . 10 . 619–34 . 10.1038/nrc.2016.71 . 27492215. 5484415 .
  7. Weber . DD . Aminzadeh-Gohari . S . Tulipan . J . Catalano . L . Feichtinger . RG . Kofler . B . Ketogenic diet in the treatment of cancer - Where do we stand? . Molecular Metabolism . March 2020 . 33 . 102–121 . 10.1016/j.molmet.2019.06.026 . 31399389. 7056920 .
  8. Pavlova . NN . Thompson . CB . The Emerging Hallmarks of Cancer Metabolism. . Cell Metabolism . 12 January 2016 . 23 . 1 . 27–47 . 10.1016/j.cmet.2015.12.006 . 26771115. 4715268 .
  9. Book: Seyfried . Thomas N. . Cancer as a metabolic disease: on the origin, management, and prevention of cancer . 2012 . Wiley . Hoboken, N.J . 978-0-470-58492-7.