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Eric Jonasch, MD, discusses the role of inhibiting hypoxia-inducible factor-2α in Von Hippel-Lindau disease–associated renal cell carcinoma.
Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the role of inhibiting hypoxia-inducible factor (HIF)-2α in Von Hippel-Lindau (VHL) disease–associated renal cell carcinoma (RCC).
Although repairing broken VHL genes would be the optimal way to treat patients with VHL disease–associated RCC, it is significantly more challenging than inhibiting HIF-2α, says Jonasch.
Inhibiting HIF-2α could be more important than inhibiting HIF-1α, Jonasch explains. However, inhibiting transcription factors offer another set of challenges as they can be difficult to target.
The potent, selective, small molecule HIF-2α inhibitor MK-6482 is the first agent to successfully block the heterodimerization of HIF-2α and its partner HIF-2β. In turn, this prevents the transcription of genes associated with angiogenesis and cell metabolism, concludes Jonasch.