PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma.

ABSTRACT: Continuous activation of hypoxia-inducible factor (HIF) is important for progression of renal cell carcinoma (RCC) and acquired resistance to antiangiogenic multikinase and mTOR inhibitors. Recently, HIF2α antagonists PT2385 and PT2399 were developed and are being evaluated in a phase I clinical trial for advanced or metastatic clear cell RCC (ccRCC). However, resistance to HIF2α antagonists would be expected to develop. In this study, we identified signals activated by HIF2α deficiency as candidate mediators of resistance to the HIF2α antagonists. We established sunitinib-resistant tumor cells in vivo and created HIF2α-deficient variants of these cells using CRISPR/Cas9 technology. Mechanistic investigations revealed that a regulator of the serine biosynthesis pathway, phosphoglyce

SUBMITTER: Yoshino H 

PROVIDER: S-EPMC5893502 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature