Post by Johan on Nov 6, 2024 11:30:26 GMT -4
Anemia is linked to poorer outcomes. Iron is essential for fundamental cellular functions and energy production.
Anemia compromises treatment effectiveness and quality of life.
Low iron levels contribute to HIF-1α stabilization.
PHDs require both oxygen and iron to function properly. In the presence of these, they hydroxylate HIF-1α, marking it for degradation. This mechanism keeps HIF-1α levels low when oxygen is plentiful.
High HIF-1α expression is associated with poorer prognoses.
Stabilizing HIF-1α could increase red blood cell production, but it would also risk further activating pro-tumorigenic pathways (Warburg effect, angiogenesis). Hence, HIF-targeted therapies for anemia need to focus on tumor-intrinsic factors rather than systemic anemia.
Stabilization of HIF-1α in normoxic conditions mimics a hypoxic state, leading to the activation of HIF-1α-regulated genes.
Copper can contribute to HIF-1α stabilization.
Hypoxic cancer cells enhance iron uptake and storage.
Tumors often have high iron requirements. Iron is used by cancer cells to support proliferation. Many cancers show altered iron homeostasis, with increased iron uptake and decreased iron export to accumulate iron, supporting rapid proliferation. This is partly achieved through upregulation of transferrin receptor 1 (TFR1) and ferroportin (FPN1) inhibition, leading to iron retention.
Iron is used by cancer cells to enhance their DNA repair capacity.
Altered iron metabolism in cancer cells contributes to immune escape by competing with immune cells for iron, suppressing anti-tumor immunity in the hypoxic tumor microenvironment.
Cancer cells’ dependency on iron makes them more vulnerable to ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation.
Ferritin storage and exosome-mediated iron export protect cancer cells from ferroptosis.
------------------------------
anticancersynergies.com/
