HIF-2–Dependent Regulation of PTHrP and Paraneoplastic Hypercalcemia in Aggressive Clear-Cell Renal Cell Carcinoma
This study uncovers a direct role for HIF-2 in driving humoral HC of malignancy in ccRCC through transcriptional activation of PTHLH (encoding PTHrP), identifies HC (and PTHrP) as potentially predictive biomarkers of HIF-2 engagement, and sets a foundation for the evaluation of HIF-2 antagonists for HC management in patients.
Authors
- Vanina Toffessi Tcheuyap (ORCID: https://orcid.org/0000-0002-6817-9241)
- Sangeetha M. Reddy (ORCID: https://orcid.org/0000-0002-8401-1481)
- Jeffrey Miyata (ORCID: https://orcid.org/0000-0001-8278-3026)
- Alana L. Christie (ORCID: https://orcid.org/0000-0002-7034-818X)
- Xiankai Sun (ORCID: https://orcid.org/0000-0002-5140-6110)
- Bingqing Xie (ORCID: https://orcid.org/0000-0001-9246-9321)
- Hua Zhong (ORCID: https://orcid.org/0000-0003-1962-2603)
- Ram S. Mani (ORCID: https://orcid.org/0000-0003-3552-7905)
- Iván Pedrosa (ORCID: https://orcid.org/0000-0002-0371-8689)
- Zane Gray (ORCID: https://orcid.org/0009-0003-1038-6787)
- Susmita G. Ramanand (ORCID: https://orcid.org/0000-0001-9711-0342)
- James Brugarolas (ORCID: https://orcid.org/0000-0002-8575-499X)
- John D. Minna (ORCID: https://orcid.org/0000-0002-7776-0767)
- Boning Gao (ORCID: https://orcid.org/0000-0002-1382-395X)
- Naim M. Maalouf (ORCID: https://orcid.org/0000-0002-0997-283X)
- Sashi Debnath (ORCID: https://orcid.org/0000-0002-0346-579X)
- Payal Kapur (ORCID: https://orcid.org/0000-0002-4239-0495)
- Yunpeng Gao (ORCID: https://orcid.org/0000-0003-4746-4614)
- Arijit Mal (ORCID: https://orcid.org/0000-0002-3960-2805)
- Jay Lohrey
- Brian Jackson
- C. J. Small
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Southwestern Medical Center (US)
- Advanced Imaging Research (United States) (US)
- Southwestern Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1158/2159-8290.cd-25-0638
- Citations
- 3
- Primary Topic
- Bone health and treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.14