How histone methyltransferases shape hormone-driven breast and prostate cancers and treatment response
Mechanisms by which histone methyltransferases regulate nuclear receptor activity and response to therapy in hormone-driven tumors.
This research looks at whether targeting a gene regulator called KMT2D can help estrogen- or androgen-driven breast and prostate cancers respond better to PI3K/AKT-targeted therapies.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Johns Hopkins University NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project ID | NIH-11264912 on NIH RePORTER |
What this research studies
Researchers will study how the histone methyltransferase KMT2D controls estrogen receptor (ER) and androgen receptor (AR) activity in hormone-driven breast and prostate cancers. They will use lab-grown cancer cell lines, animal tumor models, and patient-derived organoids to see how blocking the PI3K/AKT pathway changes KMT2D activity and receptor-driven tumor growth. The team will examine biochemical changes such as KMT2D phosphorylation by AKT1/SGK1 and test whether loss or inhibition of KMT2D makes tumors more sensitive to PI3K/AKT inhibitors. Results are intended to point to combination treatment approaches or biomarkers that could improve response to therapy.
Who could benefit from this research
Good fit: People with hormone receptor–positive breast or prostate cancer, especially tumors with PI3K pathway alterations like PIK3CA mutations, would be the most relevant candidates for related clinical efforts.
Not a fit: Patients whose tumors are not driven by estrogen or androgen receptors, or who lack PI3K pathway alterations, are less likely to benefit from approaches focused on KMT2D/PI3K crosstalk.
Why it matters
Potential benefit: Could identify combination strategies or biomarkers that overcome resistance and help ER+ breast and AR+ prostate cancers respond better to targeted therapies.
How similar studies have performed: Preclinical data and patient-derived organoid results suggest KMT2D loss can sensitize tumors to PI3K/AKT inhibitors, but clinical testing of KMT2D-targeted strategies remains novel and unproven.
Where this research is happening
Baltimore, United States
- Johns Hopkins University — Baltimore, United States (Active)
Researchers
- Principal investigator: Toska, Eneda — Johns Hopkins University
- Study coordinator: Toska, Eneda
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.