Triple-Negative Breast Cancer (TNBC)
Triple-Negative Breast Cancer (TNBC) is a highly aggressive form of breast cancer characterized by the absence of ER, PR, and HER2 receptors. Our company, a leading player in the field, provides comprehensive TNBC drug and therapy development services, including diagnostics development, therapy development, animal model development, and preclinical research.
Overview of Triple-Negative Breast Cancer
Triple-Negative Breast Cancer (TNBC) is a distinct subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. This subtype primarily affects younger women and exhibits a higher prevalence in African-American and Hispanic populations. TNBC constitutes approximately 15-20% of all breast cancer cases and is associated with a poorer prognosis compared to other subtypes.
Pathogenesis of Triple-Negative Breast Cancer
The exact cause of TNBC remains unclear, but researchers believe that genetic mutations and alterations play a significant role. In some cases, TNBC may be associated with inherited gene mutations such as BRCA1 and BRCA2, which are also linked to increased risk of ovarian cancer. Other genetic changes, including PTEN, CDH1, PIK3CA, and TP53 mutations, have been observed in TNBC, further contributing to its aggressive nature. Environmental factors may also increase the risk of developing TNBC.
Fig. 1 Progress in the classification of TNBC molecular types. (Fanale, Daniele, et al., 2020)Therapies of Triple-Negative Breast Cancer
- Chemotherapy
Due to the aggressive nature of TNBC, combination chemotherapy regimens are often employed to achieve optimal outcomes. Drugs commonly used in TNBC chemotherapy include anthracyclines (e.g., doxorubicin), taxanes (e.g., paclitaxel), and platinum agents (e.g., cisplatin). These drugs target rapidly dividing cancer cells and aim to eradicate the tumor. - Targeted Therapy
Targeted therapy is being developed to specifically address the molecular alterations present in TNBC. Such as PARP inhibitors have shown promise in BRCA1/2-mutated TNBC. Other targeted agents, such as PI3K inhibitors, AKT inhibitors, and mTOR inhibitors, are being investigated in trials to exploit the dysregulated signaling pathways in TNBC. However, targeted therapies in TNBC are still evolving, and their efficacy needs to be further validated. - Immunotherapy
Immunotherapy has revolutionized the therapeutics landscape of various cancers, and TNBC is no exception. The immune checkpoint inhibitor pembrolizumab, targeting PD-L1, has shown encouraging results in a subset of TNBC cases with high PD-L1 expression. This therapy unleashes the body's immune system to recognize and attack cancer cells. Combination approaches, such as combining immune checkpoint inhibitors with chemotherapy or other targeted agents, are being explored to enhance the response rates and overall survival outcomes in TNBC cases.
Table 1 Ongoing trials of antibody-drug conjugates in TNBC. (Zagami, Paola, et al., 2022)
| Drug | Anti-body | Target | Drug combination |
| Datopotamab deruxtecan (Dato-DXd) | Datopotamab | TROP2 | Single agent / + Durvalumab / +AZD5305(oral PARPi) |
| Sacituzumab govitecan (IMMU-132) | Sacituzumab | TROP2 | Single agent / + Avelumab / +/− Pembrolizumab + Talazoparib / + Atezolizumab |
| Ladiratuzumab vedotin (SGN-LV1a) | Ladiratuzumab | LIV1 | Single agent / + Pembrolizumab / + Atezolizumab |
| SKB264 | TROP2 | Single agent | |
| Patritumab Deruxtecan (U3-1402) | Patritumab | HER3 | Single agent |
| Trastuzumab Deruxtecan (T-DXd) | Trastuzumab | HER2 | Single agent / + Pembrolizumab / + Chemo or immunoagentse / + Durvalumab |
| Zilovertamab Vedotin (MK-2140) (VLS-101) | Zilovertamab | ROR1 | Single agent |
| Enfortumab Vedotin | Enfortumab | nectin-4 | Single agent |
| SGN-CD228A | anti-CD228 | Melanotransferrin (CD228) | Single agent |
| ASN004 | Anti-5T4 | 5T4 oncofetal antigen (trophoblast glycoprotein) | Single agent |
| CX-2009 | Anti-CD166 | CD166 | Single agent / +/−CX-072(pacmilimab)(PDL1i) |
| FDA018-ADC | Anti-TROP2 | TROP2 | Single agent |
| OBT076 (MEN1309) | Anti-CD205 | CD205 | Single agent |
| MRG002 | anti-HER2IgG1 | HER2 | Single agent |
| NBE-002 | Anti-ROR1 | ROR1 | Single agent |
| MORAb-202 | Anti-FRα | Folate Receptor Alpha (FRα) | Single agent |
| MGC018 | Anti-B7-H3 | B7-H3 | +/− Anti-PD1 (MGA012) |
| CAB-ROR2-ADC (BA3021) | Anti-CAR- ROR2 | CAB | +/− Pembrolizumab |
| PTK7-ADC (PF-06647020) | Cofetuzumab | PTK7 | + Gedatolisib |
| Trastuzumab Duocarmazine (SYD985) | Trastuzumab | HER2 | + Paclitaxel |
Our Services
At our company, we are committed to advancing TNBC diagnostics and therapy development through our comprehensive services. Our diagnostics division focuses on identifying key molecular markers and genetic alterations in TNBC tumors.
Therapy Development Platforms
Animal Models of Triple-Negative Breast Cancer
Animal models play a crucial role in understanding the biology of TNBC and evaluating the efficacy and safety of potential therapies. Our company specializes in the development of animal models, which closely mimic the characteristics of human TNBC tumors.
| Genetic Engineering Model Development | |
| Utilizing state-of-the-art genetic engineering techniques, Our company offers GEMMs that replicate key molecular alterations observed in TNBC. For instance, our murine model incorporates the amplification of the oncogene MYC and deletion of the tumor suppressor PTEN, accurately reflecting the histological and molecular features commonly found in human TNBC. | |
| Optional Modifier Genes | MYC, PTEN, Others |
| Optional Species | Mouse, Rat, Others |
In addition, we also provide other customized animal models to meet diverse needs. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Yin, Li, et al. "Triple-negative breast cancer molecular subtyping and treatment progress." Breast Cancer Research 22 (2020): 1-13.
- Zagami, Paola, and Lisa Anne Carey. "Triple negative breast cancer: Pitfalls and progress." NPJ Breast Cancer 8.1 (2022): 95.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.