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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.

Advancements have been made in the classification of molecular subtypes of 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.

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