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Updated: Dec 10, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams
Francesco P Cammarata1,2, Giusi I Forte1,2, Giuseppe Broggi3
1Institute of Molecular Bioimaging and Physiology (IBFM-CNR), 90015 Cefalù (Palermo), Italy.
Abstract:
Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.
Insights
Proton therapy (PT) shows promise for treating triple-negative breast cancer (TNBC). A 9 Gy dose of PT effectively triggered pro-death signaling in TNBC xenografts, offering a targeted treatment option.
Area of Science:
- Oncology
- Radiotherapy
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) lacks effective treatments due to its aggressive nature and negative receptor status (ER, PR, HER2).
- Proton therapy (PT) is a promising radiation technique for radio-resistant and difficult-to-access tumors.
Purpose of the Study:
- To investigate the in vivo molecular response and efficacy of proton therapy (PT) in a triple-negative breast cancer (TNBC) xenograft model.
- To identify molecular pathways and key molecules involved in cellular response to PT in TNBC.
Main Methods:
- TNBC xenograft models were irradiated with varying doses of proton therapy (2, 6, and 9 Gy).
- Gene expression profiling (GEP) and immunohistochemical assays (IHC) were employed to analyze molecular changes.
Main Results:
- Proton therapy induced significant molecular responses in TNBC, including immune response, cell cycle regulation, and stem cell processes.
- A 9 Gy dose of PT was found to shift the cellular balance towards pro-death signaling pathways.
- Proton therapy allows for dose escalation while sparing surrounding healthy tissues.
Conclusions:
- Proton therapy demonstrates potential as an effective treatment modality for triple-negative breast cancer.
- Dose escalation with proton therapy can enhance anti-tumor effects by promoting cell death signaling.
- PT's ability to target tumors precisely makes it a valuable option for TNBC management.
