Why a protein-recycling system causes treatment resistance in small cell lung cancer
Official title: Understanding the molecular mechanism of a protein-recycling complex in small cell lung cancer treatment resistance.
Funded at University Health Network · NIH-11135364 · Data updated 2026-11-12
Researchers are looking at whether problems in a protein-recycling complex make small cell lung cancer resistant to platinum chemotherapy and PARP inhibitor drugs, to help people whose cancer returns after treatment.
Quick facts
| Grant type | U01 cooperative agreement |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University Health Network NIH-funded |
| Lab location | 1 site (Toronto, Canada) |
| Project start | September 25, 2020 |
| Project end | August 31, 2026 |
| Funding year | 2025 |
| Award (this year) | $246,062 |
| NIH project number | 5U01CA253383-05 |
| Project ID | NIH-11135364 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with small cell lung cancer—especially those whose cancer has relapsed after platinum-based chemotherapy or who are being considered for PARP inhibitor therapy—are the most likely candidates to participate or benefit.
✕Less likely to help
People without small cell lung cancer or whose tumors do not show the specific protein-recycling defect identified here are unlikely to benefit directly from this research.
What this research studies
I have small cell lung cancer and the treatments that usually work sometimes stop working because the cancer becomes resistant. This project used a large-scale CRISPR genetic screen and laboratory experiments to find parts of a protein-recycling (SCF) complex that drive resistance to PARP inhibitors and platinum chemotherapy. The team validated their findings in cell models and compared them to genetic changes in patient relapse tumors, identifying loss of an F-box protein that may explain resistance in up to about 20% of relapsed cases. They aim to turn this knowledge into biomarkers and new approaches to overcome treatment resistance.
Why it matters
Potential benefit: If successful, this work could help predict which SCLC patients are unlikely to respond to PARP inhibitors or platinum drugs and point to new therapies that overcome resistance.
How similar studies have gone: PARP inhibitors are effective in BRCA-mutant cancers and CRISPR screens have revealed resistance mechanisms in other settings, but linking an F-box protein deficiency to PARP and cisplatin resistance in SCLC is a novel finding.
Where this research is happening
-
University Health Network
Toronto, Canada Active
Researchers
- Principal investigator: Lok, Benjamin H — University Health Network
- Study coordinator: Lok, Benjamin H
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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.