Similarly, tumors with an intact tumor suppressor gene known as p53 respond more readily to radiation and to HIF-1 inhibition than tumors with a mutated P53 gene. Understanding such factors can aid scientists in determining the best conditions under which to inhibit HIF-1.
"We want to maximize the benefits of HIF-1 blockage while minimizing the drawbacks," said Moeller.
Moeller used a unique, targeted approach of blocking HIF-1 in cells to ensure that HIF-1, and not other proteins, was responsible for the effects they saw. He inserted a mutated form of HIF-1 into the cancer cell and turned it on and off by exposing it to the antibiotic tetracycline.
With this reversible switch, the team could observe the effects while HIF-1 was active and when it was blocked. Drugs to block HIF-1 have been used in previous studies conducted at Duke and elsewhere, but such drugs inhibit other proteins as well, making it impossible to distinguish which effects are related to HIF-1 and which are not.
The team's next step is to test the effects of blocking HIF-1 following chemotherapy. The research was funded by the National Cancer Institute, the Howard Hughes Medical Institute and the Aeolus Corporation.