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Can Fasting Make Less Toxic Cancer Drugs More Potent?

Last updated April 30, 2015

Destroyer of furries

Short-term fasting renders the cancer cells unable to survive and potentiates the effect of less toxic cancer drugs to block cancer growth.

Yes, says two new studies conducted on cancer models of mice. The results showed that short-term fasting renders the cancer cells unable to survive and potentiates the effect of less toxic cancer drugs to block cancer growth. These research articles are based on the work of Dr. Valter Longo of the University of Southern California and several co-researchers.

Malignant cancer cells usually consume glucose by a different pathway than normal cells, giving them the energy to grow rapidly. This phenomenon is called the “Warburg effect.” This makes the cancer cells more vulnerable to energy deprivation. When the energy supply is restricted to cancer cells, they resort to a different pathway to survive. However, this pathway of generating energy, which employs a class of enzymes called “tyrosine kinases,” also produces free radicals. Free radicals are toxic to cells, and this leads to the destruction of cancer cells.

Many cancer drugs have been designed and are in use to inhibit tyrosine kinase (Tyrosine Kinase Inhibitors or TKIs) to restrict the growth of cancer cells. TKIs are less toxic and, therefore, have fewer side effects. However, their effect is short-lived and scientists are constantly searching for ways to potentiate these drugs.

Previous studies by Dr. Longo have shown that:

  • Cycles of fasting/feeding in mice reverses immunosuppression brought on by chemotherapy drugs, indicating a protective effective of fasting on immune cells
  • In older mice, there was stem-cell based regeneration of blood cells
  • In a mouse model of brain cancer, controlled fasting sensitized cancer cells to radiation and chemotherapy.

With this background, in the latest study, Dr. Longo and fellow scientists have combined fasting with the less toxic TKI treatment in mice with cancer. The results indicate that TKI treatment in starving mice produced the most optimum anti-cancer outcome. In the authors’ own words, “This work highlights a possible new application for fasting (or for specifically designed fasting-mimicking diets) in oncology in combination with TKIs which has the potential to reduce toxicity to the host while enhancing the efficacy of the therapy.”

Clinical trials are ongoing to test if short-term fasting may protect normal cells from the side effects of chemotherapy, sponsored by the National Cancer Institute and Mayo Clinic.

Written by Mangala Sarkar Ph.D.

Primary References:

Bianchi, G., Martella, R., Ravera, S., Marini, C., Capitanio, S., Orengo, A., Emionite, L., Lavarello, C., Amaro, A., Petretto, A., Pfeffer, U., Sambuceti, G., Pistoia, V., Raffaghello, L., & Longo, V. (2015). Fasting induces anti-warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models. Oncotarget, 5. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3688

Caffa, I., D’Agostino, V., Damonte, P., Soncini, D., Cea, M., Monacelli, F., Odetti, P., Ballestrero, A., Provenzani, A., Longo, V., & Nencioni, A. (2015). Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget, 5. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3689

Additional References:

Vander Heiden, M., Cantley, L., & Thompson, C. (2009). Understanding The Warburg Effect: The Metabolic Requirements Of Cell Proliferation. Science, 324(5930), 1029-1033.

Krause, D., & Etten, R. (2005). Tyrosine Kinases as Targets for Cancer Therapy. New England Journal of Medicine, 353(2), 172-187.

Cheng, C., Adams, L., Perin, G., Wei, M., Zhou, X., Lam, B., . . . Longo, V. (2014). Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression. Cell Stem Cell, 14(6), 810-823.

Safdie F, Brandhorst S, Wei M, Wang W, Lee C, et al. (2012) Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy. PLoS ONE 7(9): e44603. doi:10.1371/journal.pone.0044603

Brandhorst, S., Wei, M., Hwang, S., Morgan, T., & Longo, V. (2013). Short-term calorie and protein restriction provide partial protection from chemotoxicity but do not delay glioma progression. Experimental Gerontology, 48(10), 1120-1128.

Clinical Trials (PDQ®). (n.d.). Retrieved April 28, 2015, from http://www.cancer.gov/clinicaltrials/search/view?cdrid=683360&version=HealthProfessional

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: April 30, 2015
Last updated: April 30, 2015