Targeting HIF-1α promotes ferroptosis and boosts antitumor immunity in MSS colorectal cancer - PubMed
6 hours ago
- #ferroptosis
- #colorectal cancer
- #HIF-1α
- MSS colorectal cancer lacks effective treatments, and chemotherapy-resistant cells can be induced into ferroptosis.
- RSL3, a ferroptosis inducer, suppressed MSS CRC cell growth, but some cells showed resistance linked to hypoxia pathway activation.
- Inhibiting HIF-1α restored RSL3 sensitivity in resistant cells, while HIF-1α overexpression reduced it, with HIF-1α promoting P4HA1 expression to drive resistance.
- In mice, combining RSL3 with an HIF-1α inhibitor enhanced tumor suppression and metastasis prevention, increased immune cell infiltration, and improved anti-PD1 response.
- Targeting HIF-1α alongside ferroptosis inducers is a promising strategy for MSS CRC treatment.