Determinants of Response to DNA-Damaging Radiation and Immunotherapy in Triple-Negative Breast Cancer
Official title: Project 2: Determinants of Response and Resistance to DNA-Damaging Radiation Plus Immunotherapy Combinations in Triple Negative Breast Cancer
Funded at Univ of North Carolina Chapel Hill · NIH-11411395 · Data updated 2026-11-12
This grant explores why some people with triple-negative breast cancer respond to a combo of radiation, chemotherapy, and immunotherapy and why others don’t, to guide more personalized treatment.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of North Carolina Chapel Hill NIH-funded |
| Lab location | 1 site (Chapel Hill, United States) |
| Project start | August 5, 1997 |
| Project end | August 31, 2029 |
| Funding year | 2026 |
| Award (this year) | $350,106 |
| NIH project number | 5P50CA058223-31 |
| Project ID | NIH-11411395 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with early-stage triple-negative breast cancer, especially those with lymph node involvement, who may be eligible for preoperative anti-PD1 therapy with or without radiation.
✕Less likely to help
Patients without the relevant biomarkers or those not receiving chemo-immunotherapy as part of the studied regimens may see no benefit.
What this research studies
Researchers will study how DNA damage and immune system interactions influence treatment outcomes in early-stage triple-negative breast cancer. They will use mouse models and analyses of tumor samples and blood from a clinical trial to find biomarkers that predict who benefits from DNA-damaging radiation plus anti-PD1 therapy. The work aims to define a gene signature of necroptosis proficiency and test whether this signature can forecast tumor and immune changes after treatment. They also plan to investigate whether radiation and anti-PD1 therapy trigger systemic immune responses and if neoantigen vaccination could overcome resistance. The project seeks to translate findings into more effective, personalized chemo-immunotherapy strategies for TNBC patients.
Why it matters
Potential benefit: If successful, this research could lead to better patient selection and new strategies to make chemo-immunotherapy work more often and with fewer failures.
How similar studies have gone: Early studies suggest that biomarkers of necroptosis and neoantigen-directed responses can influence immunotherapy outcomes, but this specific combination with RT and PD-1 blockade in TNBC is ongoing and exploratory.
Where this research is happening
-
Univ of North Carolina Chapel Hill
Chapel Hill, United States Active
Researchers
- Principal investigator: Gupta, Gaorav P. — Univ of North Carolina Chapel Hill
- Study coordinator: Gupta, Gaorav P.
Related research
Other NIH-funded projects on the same topics.
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Rac-enhanced CAR-Macrophages against TNBC
A new cell therapy approach uses engineered macrophages with a CAR and Rac2 activation to target and kill triple-negative breast cancer cells expressing CSPG4.
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New immunotherapy combo for hard-to-treat triple-negative breast cancer
Aims to test a combination immunotherapy with JNK inhibitors to improve treatment for people with triple-negative breast cancer.
-
Reprogrammed exosome immunotherapy for triple-negative breast cancer
A new treatment approach uses engineered exosomes to stimulate the immune system to fight triple-negative breast cancer in patients.
-
Engineered CD4+ T cells targeting KK‑LC‑1 for triple‑negative breast cancer
This project creates engineered CD4+ T cells that recognize the KK‑LC‑1 tumor antigen to help people with HLA‑DR13-positive triple‑negative breast cancer.
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Why some triple-negative breast cancers respond to radiation plus immunotherapy and others resist
This project looks at whether patterns of tumor cell death and immune signals can predict and improve responses to radiation combined with anti-PD1 immunotherapy for people with early-stage triple-negative breast cancer that has spread to lymph nodes.
-
New combination immunotherapy for triple-negative breast cancer
See if adding a drug that blocks the JNK pathway can help immunotherapy work better for people with triple-negative breast cancer.
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.