Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes of breast cancer. Unlike other breast cancer subtypes, TNBC lacks expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), which poses significant challenges in the development of effective therapies. At Alfa Cytology, our team of experienced biologists work with you to develop TNBC therapeutics.
Introduction to Triple-Negative Breast Cancer (TNBC)
TNBC accounts for approximately 15-20% of all breast cancer cases and is more prevalent in younger women, African American women, and those with BRCA1 mutations. Clinically, TNBC is associated with an increased risk of recurrence, metastatic disease, and shorter overall survival compared to other breast cancer subtypes. This is largely due to the absence of targeted therapies, such as endocrine therapy and HER2-directed agents, which have revolutionized the treatment of hormone receptor-positive and HER2-positive breast cancers, respectively.
Fig.1 Classifcation and therapeutic options for TNBC. (Li Y., et al. 2022)
Therapy Development for Triple-Negative Breast Cancer (TNBC)
TNBC is a highly heterogeneous cancer with specific mutations and aberrant activation of signaling pathways. Therefore, targeted therapies (e.g., therapies targeting DNA repair pathways, androgen receptor signaling pathways, and kinases) are promising options for the treatment of TNBC. In addition, immunotherapy has been shown to improve overall survival and response rates in TNBC. We summarize important recent advances in therapeutic strategies based on the molecular subtypes of TNBC.
| Category | Target | Therapeutics | Register ID | Phase |
| Molecularly Targeted Therapies | Cell cycle | PF-06873600 | NCT03519178 | |
| Microtubule dynamics | Eribulin mesylate | NCT04502680 | ||
| VEGF/VEGFR | Anlotinib | NCT04452370 | ||
| EGFR | SCT200 | NCT03692689 | ||
| PI3K/AKT/mTOR | Alpelisib with nab-paclitaxel | NCT04251533 | ||
| HDAC | Entinostat | NCT02708680 | ||
| Immunotherapy | / | TQB2450 | NCT04405505 | |
| PD-1 | HLX10 | NCT04301739 | ||
| Adoptive Cell Therapy | / | ROR1-targeted CAR T cell (LYL797) | NCT05274451 | |
| / | CART-TnMUC1 cells | NCT04025216 | ||
| / | PD-1+ TILS | NCT05451784 | ||
| / | TC-510 | NCT05451849 |
Our Services
At Alfa Cytology, we offer a comprehensive suite of preclinical services to support the development of novel TNBC therapies. Our state-of-the-art facilities and experienced team of scientists provide a wide range of in vitro and in vivo capabilities, including:
TNBC Therapy Development Platforms
Disease Models of TNBC
Through rigorous research and collaboration with experts in the field, we aim to identify novel therapeutic targets and develop innovative drugs that can effectively treat TNBC while minimizing side effects. Our company's expertise in drug development, including preclinical research and model development, allows us to accelerate pharmaceutical companies' research and development.
 TNBC Cell Lines |
 Animal Models of TNBC |
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Case Study
A C57BL/6J Mouse 4T1-LUC Breast Cancer Model for Nanomedicine Evaluation
- Model Introduction
The C57BL/6J mouse 4T1-LUC breast cancer model is a highly valuable and aggressive syngeneic model for studying triple-negative breast cancer (TNBC) progression, metastasis, and immunotherapy. This model closely recapitulates the stage-wise progression and high metastatic potential observed in human breast cancer, making it particularly suitable for evaluating novel nanomedicine-based therapeutic strategies.
- Model Information
- Model: C57BL/6J Mouse 4T1-LUC Breast Cancer Model
- Cancer Type: Triple-Negative Breast Cancer (TNBC)
- Host Mouse Strain: C57BL/6J Mice
- Age: 6-8 Weeks
- Cell Line Origin: 4T1 murine mammary carcinoma cells stably expressing luciferase (LUC).
- Molecular Profile: Triple-negative (ER-, PR-, HER2-); highly aggressive and metastatic.
- Weight: 18-22 g
- Model Construction
The 4T1-LUC model was established by orthotopically implanting 4T1-LUC cells into the mammary fat pads of C57BL/6J mice. Tumor growth was monitored using bioluminescence imaging, and mice were randomized into treatment groups when tumors reached a predefined volume to initiate efficacy studies.
Fig. 2 Schematic diagram of C57BL/6J mouse 4T1-LUC breast cancer model establishment and treatment plan. (Source: Alfa Cytology)
- In Vivo Efficacy Evaluation
This case employed the 4T1-LUC model to systematically evaluate a nanodrug co-delivering antibiotic drug A and photosensitizer drug B, both as monotherapy and in combination with laser irradiation.
- Potent Tumor Suppression: The combination of drug A + drug B nanodrug with laser irradiation resulted in the most significant inhibition of primary tumor growth among all experimental groups, demonstrating powerful synergistic therapeutic activity.
- Effective Tumor Microenvironment Remodeling: Flow cytometry analysis demonstrated successful immune activation, characterized by a significant increase in tumor-infiltrating cytotoxic T lymphocytes (CTLs) and repolarization of tumor-associated macrophages to tumoricidal M1-type macrophages.
Fig. 3 Efficacy of nanomedicines in 4T1-LUC CDX models. Data show the mean ± standard error of the treatment with drug A, drug B, or drug A + drug B nanomedicine (n = 6). (Source: Alfa Cytology)
We are committed to collaborating with healthcare providers and researchers to drive meaningful progress in this critical area of breast cancer management. By collaborating with Alfa Cytology, clients gain access to a comprehensive suite of services tailored to the unique needs of TNBC research and therapeutic development. If you are interested in our service, please contact us.
Reference
- Li Y., Zhang H., and et al. Recent advances in therapeutic strategies for triple-negative breast cancer. J Hematol Oncol. 2022, 15(1): 121.