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Review
. 2014 Nov;29(6):391-8.
doi: 10.5001/omj.2014.107.

Starvation Based Differential Chemotherapy: A Novel Approach for Cancer Treatment

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Free PMC article
Review

Starvation Based Differential Chemotherapy: A Novel Approach for Cancer Treatment

Sidra Naveed et al. Oman Med J. .
Free PMC article

Abstract

Cancer patients undergoing chemotherapy treatment are advised to increase food intake to overcome the therapy-induced side effects, and weight loss. Dietary restriction is known to slow down the aging process and hence reduce age-related diseases such as cancer. Fasting or short-term starvation is more effective than dietary restriction to prevent cancer growth since starved cells switch off signals for growth and reproduction and enter a protective mode, while cancer cells, being mutated, are not sensitized by any external growth signals and are not protected against any stress. This phenomenon is known as differential stress resistance (DSR). Nutrient signaling pathways involving growth hormone/insulin-like growth factor-1 axis and its downstream effectors, play a key role in DSR in response to starvation controlling the other cell maintenance systems, such as autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells lacking these effectors are better protected against oxidative stress compared to normal cells. In the same way, starvation protects many cell lines and mice against high-dose chemotherapeutic drugs. According to a series of studies, fasting results in overall reduction in chemotherapy side effects in cancer patients. Data shows that starvation-dependent differential chemotherapy is safe, feasible and effective in cancer treatment, but the possible side effects of starvation limit its efficacy. However, further studies and clinical trials may result in its implementation in cancer treatment.

Keywords: Dietary restriction; Differential chemotherapy; Differential stress resistance; Nutrient-signaling pathways; Starvation.

Figures

Figure 1
Figure 1
Starvation-induced differential stress resistance. Starvation decreases serum insulin-like growth factor 1 (IGF-1) levels, and growth factors, which further affect downstream growth regulators mammalian target of rapamycin (mTOR), Akt and Ras. In cancer cells these regulators are activated in response to reduced IGF-1, increasing oxidative stress leading to DNA, damage and eventually cell death in the presence of chemotherapy drugs.

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