The Insulin Receptor: A New Target for Cancer Therapy

(Steve Stephenson) #1

Cancer cells often overexpress both IGF-IR and IR

Since the activation of the Ras pathway mediates cellular mitogenic responses, the effect of insulin in increasing the pool of farnesylated p21Ras amplifies the mitogenic effects of insulin itself and other growth factors, such as IGF-I. This mechanism could explain the exaggerated mitogenic response to growth factors in patients with high levels of circulating insulin

As mentioned before, the long-term exposure to hyperinsulinemia consequent to insulin resistance provides a link between diabetes, obesity, and cancer.

Cancer in a remission!
(Bunny) #2

Some additional points of interest:

“…However, only very few drugs acting as insulin sensitizers or IR inhibitors are currently available for clinical treatments and we expect that more options will be accessible in the near future. We are just starting to learn how and when using these two classes of drugs either alone or in combination in cancer patients . …”

Glucose released from glycogen is their a difference? Can daf-2 worms reaction cross over to humans?

  1. Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress
    “…Moreover, glycogen interferes with low insulin signaling and accelerates aging of long-lived daf-2 worms fed a high glucose diet. Considering its extensive evolutionary conservation, our results suggest that glycogen metabolism might also have a role in mammalian aging. …” “…Glucose released from glycogen and used for NADPH/glutathione reduction renders nematodes and human hepatocytes more resistant against oxidative stress. …”
  1. Glucose Induces Sensitivity to Oxygen Deprivation and Modulates Insulin/IGF-1 Signaling and Lipid Biosynthesis in Caenorhabditis elegans “…Our studies show that a glucose-supplemented diet negatively impacts oxygen deprivation survival and significantly alters gene expression profiles in C. elegans. Genetic suppression analysis of the known stress-resistant mutant daf-2(e1370) revealed that antioxidant, fatty acid biosynthesis and ceramide synthesis are essential for the animal to survive anoxia when fed a glucose-supplemented diet. …”
  1. Glucagon and/or IGF-1 Production Regulates Resetting of the Liver Circadian Clock in Response to a Protein or Amino Acid-only Diet Here we report that both dietary protein and cysteine alone entrain liver circadian rhythm by increasing glucagon and/or IGF-1 levels independently of insulin.
  1. Impact of metabolic disorders on prostate cancer growth: Androgen and insulin resistance perspectives Certain drugs for T2DM treatment, such as metformin and glucagon‐like peptide‐1 analog, potentially might be useful for the treatment of PC.