How VHL gene changes drive clear cell kidney cancer and new ways to target them
Official title: The von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable Mutations
Funded at Dana-Farber Cancer Inst · NIH-11173812 · Data updated 2026-11-12
This project is developing new drug approaches that exploit weaknesses in tumors caused by VHL or IDH mutations to help people with clear cell kidney cancer and other cancers with these mutations.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | September 1, 2016 |
| Project end | August 31, 2030 |
| Funding year | 2025 |
| Award (this year) | $997,800 |
| NIH project number | 5R35CA210068-10 |
| Project ID | NIH-11173812 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with clear cell renal cell carcinoma caused by VHL loss, and patients with IDH-mutant cancers needing new therapy options, would be the most relevant candidates for eventual trials based on this work.
✕Less likely to help
Patients with cancers not driven by VHL or IDH mutations, or those looking for immediate clinical therapy, are unlikely to receive direct benefit from this lab-focused research right away.
What this research studies
If you or someone you care for has clear cell kidney cancer, this project is working to find new drug targets caused by VHL or related IDH mutations. The team uses laboratory experiments, genetic screens, biochemical assays, and animal models to find proteins the tumor depends on, such as CDK4/6 or ITGAV, and to test drugs that block or destroy those proteins. The researchers build on past work that led to VEGF and HIF2 inhibitors and are focusing on 'synthetic lethality'—targeting partner vulnerabilities in tumors with undruggable mutations. Promising findings could point to new drug combinations and eventually lead to clinical trials at Dana‑Farber or collaborating centers.
Why it matters
Potential benefit: Could identify new treatment targets or drug combinations for people whose VHL-driven kidney cancers or IDH-mutant tumors do not respond to current therapies.
How similar studies have gone: Related discoveries from this team helped produce VEGF and HIF2 inhibitors and IDH blockers that benefit some patients, but applying synthetic lethality to target VHL or IDH tumors is a newer approach still being developed.
Where this research is happening
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Dana-Farber Cancer Inst
Boston, United States Active
Researchers
- Principal investigator: Kaelin, William G. — Dana-Farber Cancer Inst
- Study coordinator: Kaelin, William G.
Related research
Other NIH-funded projects on the same topics.
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Maximizing anti-tumor immune responses in kidney cancer
A cutting-edge program at UT Southwestern aims to speed up better immunotherapy options for kidney cancer by studying how to activate both innate and adaptive immune responses.
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Kidney Cancer Career Enhancement Program (CEP) at DF/HCC
A career-boosting program supports junior investigators studying kidney cancer to help them advance in basic, translational, and clinical work.
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Kidney Cancer Development Program at DF/HCC
A funded program at Dana-Farber/Brigham and Women’s Kidney Cancer Center supports new ideas from researchers to improve understanding and treatment of kidney cancer.
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Personalized antigens for kidney cancer therapy
This grant explores identifying and targeting tumor-specific antigens in kidney cancer to develop more effective, personalized immunotherapies.
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Optimizing Anti-PD1 Therapy for High-Risk and Metastatic Kidney Cancer
A large cancer research grant is testing how best to use anti-PD-1 therapy to help people with high-risk and metastatic kidney cancer live longer and with fewer side effects.
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Targeting the HIF2 Pathway in Kidney Cancer
A cancer treatment program aims to see if a drug called belzutifan can help people with a specific kind of kidney cancer whose growth is driven by the HIF2 pathway.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.