Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index.
Level 5 - mechanism / opinion, no new human data
Animal and in vitro experimental study with no human data.
PubMed 20145127 · doi:10.1158/0008-5472.CAN-09-3228
What was done
The authors investigated whether reducing IGF-I signaling mediates fasting-induced differential stress resistance against chemotherapy. They measured circulating IGF-I and IGFBP-1 in mice after a 72-hour fast, assessed survival in liver IGF-I-deficient (LID) mice exposed to four chemotherapy agents and in melanoma-bearing LID mice treated with doxorubicin, and examined toxicity in primary glia versus glioma cells, mouse embryonic fibroblasts, and S. cerevisiae yeast lacking IGF-I signaling homologs.
What was found
A 72-hour fast in mice reduced circulating IGF-I by 70% and increased IGFBP-1 levels 11-fold. LID mice with a 70% to 80% reduction in circulating IGF-I were protected against three of four tested chemotherapy drugs, and restoring IGF-I reversed fasting protection. Sixty percent of melanoma-bearing LID mice treated with doxorubicin achieved long-term survival, whereas all control mice died of metastases or toxicity. Reduced IGF-I signaling protected primary glia (but not glioma cells) from cyclophosphamide and protected fibroblasts and yeast from chemotherapy-induced DNA damage.
Why it matters
This study identifies circulating IGF-I reduction as a key driver of fasting-mediated differential stress resistance, demonstrating that lowering IGF-I protects normal tissues against high-dose chemotherapy without protecting malignant cells. It provides mechanistic support for short-term fasting or IGF-I modulation during cancer chemotherapy.
Limits
Findings are entirely derived from in vitro cell models, yeast, and mice; clinical efficacy and safety in humans are unmeasured. The abstract does not provide exact animal sample sizes, confidence intervals, or identification of the single chemotherapy drug that failed to show protection in LID mice.
Cited by
- supports A 48-hour fast reduces circulating IGF-1 levels by approximately 50% in mice.