Hypoxia- Increasing treatment resistance in tumours
Hypoxia- Increasing treatment resistance in tumours
Hypoxia, or low oxygen levels, in the tumor microenvironment significantly contributes to treatment resistance in cancer through several mechanisms:
- Altered Cellular Metabolism: Hypoxic conditions lead to a shift in tumor cell metabolism from oxidative phosphorylation to glycolysis, known as the Warburg effect. This metabolic shift supports tumor survival and growth under low oxygen conditions and can reduce the effectiveness of treatments that target rapidly dividing cells.
- Induction of Hypoxia-Inducible Factors (HIFs): Hypoxia stabilizes HIFs, particularly HIF-1α, which are transcription factors that activate genes involved in angiogenesis, metabolism, and survival. HIFs promote the expression of vascular endothelial growth factor (VEGF), leading to angiogenesis and further supporting tumor growth and resistance to therapies.
- Reduced Drug Penetration: The abnormal vasculature and high interstitial pressure in hypoxic tumors can limit the delivery and penetration of chemotherapeutic agents, reducing their efficacy.
- Increased DNA Repair and Survival Pathways: Hypoxia can enhance the expression of genes involved in DNA repair and cell survival, making tumor cells more resistant to DNA-damaging agents like chemotherapy and radiotherapy.
- Promotion of Epithelial-Mesenchymal Transition (EMT): Hypoxia can induce EMT, a process where epithelial cells acquire mesenchymal, invasive properties. This transition is associated with increased metastatic potential and resistance to apoptosis, contributing to treatment resistance.
- Immune Evasion: Hypoxic conditions can alter the tumor microenvironment to suppress immune responses, making immunotherapies less effective. Hypoxia can impair the function of immune cells and promote the recruitment of immunosuppressive cells.
Overall, hypoxia creates a challenging environment that supports tumor survival and resistance to various treatments, necessitating strategies to overcome or target hypoxic regions within tumors.