Why BRCA1 cancers become resistant to PARP inhibitor treatment
Compensatory Mechanisms that Promote Homologous Recombination in BRCA1 Mutant Cancers
Researchers aim to learn how BRCA1-related cancers regain precise DNA repair and stop responding to PARP inhibitor medicines.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Research Inst of Fox Chase Can Ctr NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11164838 on NIH RePORTER |
What this research studies
From my perspective, this work is trying to find out why some BRCA1-mutant tumors that should be sensitive to PARP inhibitors instead become resistant by restoring homologous recombination DNA repair. The team has found genes that can restore recruitment of a repair helper called PALB2 even when BRCA1 is defective. They will define which parts of PALB2 are needed for repair, figure out how other proteins block PALB2, and test whether changes in those regulators cause resistance. The findings will be checked in laboratory systems and BRCA1 mouse tumor models to see if the same mechanisms occur in cancers.
Who could benefit from this research
Good fit: Ideal candidates would be people with BRCA1-mutant cancers who have received or are considering PARP inhibitor therapy and who can provide clinical information or tumor samples.
Not a fit: People without BRCA1/BRCA2 mutations or whose cancers rely on unrelated resistance pathways may not directly benefit from these findings.
Why it matters
Potential benefit: If successful, this work could reveal new drug targets or tests to predict and overcome PARP inhibitor resistance in BRCA1-mutant cancers.
How similar studies have performed: Previous studies have shown that some tumors regain DNA repair through BRCA1 reversion mutations, but the role of PALB2-regulating genes as a resistance route is a newer area under study.
Where this research is happening
Philadelphia, United States
- Research Inst of Fox Chase Can Ctr — Philadelphia, United States (Active)
Researchers
- Principal investigator: Johnson, Neil — Research Inst of Fox Chase Can Ctr
- Study coordinator: Johnson, Neil
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.