Combining a glutamine blocker with 5‑FU for PIK3CA‑mutant colon cancer
Mechanisms of metabolic reprogramming by PIK3CA oncogenic mutations
See if adding a glutaminase blocker to standard 5‑FU helps immune cells trap and kill PIK3CA‑mutant colon cancer cells.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Case Western Reserve University NIH-funded |
| Lab location | 1 site (Cleveland, United States) |
| Project ID | NIH-11241091 on NIH RePORTER |
What this research studies
This project focuses on PIK3CA‑mutant colorectal (colon) cancers and tests a drug combination of CB‑839 (a glutaminase inhibitor) plus 5‑FU in laboratory tumor models. Researchers will use mouse models and tumor grafts to observe whether neutrophils form neutrophil extracellular traps (NETs) that can kill the cancer cells and will compare effects in tumors with and without PIK3CA mutations. They will also remove neutrophils or break up NETs to confirm whether NETs are required for the treatment effect and will study immune‑competent models to better reflect human biology. The work builds on prior preclinical results showing that the combination caused tumor regressions and induced NETs in PIK3CA‑mutant tumors.
Who could benefit from this research
Good fit: Patients with colorectal cancer whose tumors carry activating PIK3CA mutations would be the most relevant group for this approach.
Not a fit: Patients without PIK3CA mutations or those with other cancer types are unlikely to benefit from this specific combination based on the grant’s focus.
Why it matters
Potential benefit: If successful, this could point to a new way to make standard chemotherapy work better for patients with PIK3CA‑mutant colorectal cancer by using metabolism‑targeting drugs to enlist the immune system.
How similar studies have performed: Preclinical mouse and xenograft studies by the same team showed the drug combo shrank PIK3CA‑mutant tumors and induced NETs, but human clinical benefit has not yet been established.
Where this research is happening
Cleveland, United States
- Case Western Reserve University — Cleveland, United States (Active)
Researchers
- Principal investigator: Wang, Zhenghe — Case Western Reserve University
- Study coordinator: Wang, Zhenghe
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 below.