Tumor dependency on HIF-2 pathway may prove Achilles heel for kidney cancer

February 14, 2020
Announcement
Targeted Drugs, HIF2, SPORE
Left: HIF-2 complex (red dots) in kidney cancer cells (blue circles), formed when HIF-2a and HIF-1b proteins bind together, activating genes responsible for creating blood vessels, which cancer cells need to survive. Right: HIF-2 blocking drug PT2385 breaks apart the complex, as seen in on-treatment image where red dots have largely disappeared.

In a newly published study revealing the underlying efficacy of HIF-2 inhibitor drugs, investigators at UT Southwestern have discovered a potential Achilles heel for kidney cancer. 

Clinical trial findings identified a cancer core dependency on HIF-2, a protein complex that plays a key role in the activation of genes responsible for cancer growth. In response to the drug’s ability to disable HIF-2, tumors developed a resistance in the form of a mutation in the protein binding pocket where the drug is delivered, thereby preventing access to it. 

The finding suggests the critical role HIF-2 plays in the progression of kidney cancer and the extent to which tumors will safeguard it. PRESS RELEASE

Kidney Cancer Patient Spotlight:
Richard Martinez

HIF-2 is a key driver of kidney cancer. UT Southwestern investigators are credited with the discovery of the HIF-2 gene, identifying its role in promoting kidney cancer and subsequently developed a drug to inhibit it. Richard Martinez’s story highlights the drug development taking place at UT Southwestern and the clinical trials available to patients.

In a newly published study revealing the underlying efficacy of HIF-2 inhibitor drugs, investigators at UT Southwestern have discovered a potential Achilles heel for kidney cancer. Clinical trial findings identified a cancer core dependency on HIF-2, a protein complex that plays a key role in the activation of genes responsible for cancer growth. In response to the drug’s ability to disable HIF-2, tumors developed a resistance in the form of a mutation in the protein binding pocket where the drug is delivered, thereby preventing access to it. The finding suggests the critical role HIF-2 plays in the progression of kidney cancer and the extent to which tumors will safeguard it. Press Release