How a protein switch may drive ER-positive breast cancer to resist treatment and spread
Official title: A SIM2s/SEMA7A Switch Drives ER+ Breast Cancer Progression
Funded at University of Colorado Denver · NIH-11284024 · Data updated 2026-11-12
This project looks at whether changes between two proteins, SIM2s and SEMA7A, help estrogen receptor–positive (ER+) breast cancers stop responding to hormone drugs and become more aggressive.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Colorado Denver NIH-funded |
| Lab location | 1 site (Aurora, UNITED STATES) |
| Project start | March 1, 2024 |
| Project end | February 28, 2029 |
| Funding year | 2026 |
| Award (this year) | $542,378 |
| NIH project number | 5R01CA282900-03 |
| Project ID | NIH-11284024 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with ER-positive breast cancer—especially those with recurrent or metastatic disease or whose tumors show high SEMA7A—would be the most relevant candidates for related future trials or tissue-donation efforts.
✕Less likely to help
Patients with ER-negative breast cancers or those whose tumors do not involve the SIM2s/SEMA7A pathway are unlikely to benefit directly from findings focused on this specific mechanism.
What this research studies
Researchers have found that high levels of the protein SEMA7A in ER+ tumors are linked with shorter survival and poorer responses to tamoxifen. They will study how loss of the tumor suppressor SIM2s and gain of SEMA7A activate cell survival signals and epithelial-to-mesenchymal changes that can lead to therapy resistance and metastasis. The team will use tumor samples, cell models, and animal models to map the signaling pathways and test whether blocking survival pathways can restore drug sensitivity. The work aims to identify biomarkers and drug targets that could guide new treatments for people with recurrent or metastatic ER+ breast cancer.
Why it matters
Potential benefit: If successful, this work could point to new targets or biomarkers to overcome hormone-therapy resistance and slow or prevent spread in ER+ breast cancer patients.
How similar studies have gone: Previous studies have linked high SEMA7A and low SIM2s to worse outcomes and therapy resistance, but targeting this specific switch as a treatment approach is relatively novel.
Where this research is happening
-
University of Colorado Denver
Aurora, United States Active
Researchers
- Principal investigator: Lyons, Traci — University of Colorado Denver
- Study coordinator: Lyons, Traci
Related research
Other NIH-funded projects on the same topics.
-
ER+ Breast Cancer Bone Metastasis in a Real Body Environment
This grant aims to understand why estrogen receptor alpha–positive breast cancer often spreads to bone and how the bone environment and immune system affect treatment resistance.
-
Targeting RAGE to fight obesity-related ER+ breast cancer and its drug resistance
A scientist team will explore how obesity-related inflammation involving RAGE and estrone interacts with ER+ breast cancer to drive growth and spread, aiming to find strategies to overcome therapy resistance.
-
Understanding estrogen signals in bone to stop ER+ breast cancer spread
This NIH grant aims to uncover how estrogen signals inside bone help ER-positive breast cancer cells grow and spread, with the goal of finding better ways to prevent bone metastasis.
-
Progesterone Receptor Signaling and Dormancy in ER+ Breast Cancer
Researchers are studying how hormone signals in ER+/PR+ breast cancer influence cancer cell dormancy and later recurrence.
-
Heavy Metals and Breast Cancer Treatment Resistance
This project explores how exposure to heavy metals might make ER+ breast cancer harder to treat and how we might overcome this challenge.
-
Turning ER-positive breast cancer into a viral target for immune attack
This project aims to wake up viral-like bits inside ER-positive breast cancer cells so the immune system can spot and attack them.
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.