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Adenoid Cystic Carcinoma (ACC)

Adenoid cystic carcinoma (ACC) presents substantial difficulties due to its aggressive behavior, tendency for local infiltration, and frequent recurrence. Our company leads the way in delivering comprehensive solutions to pharmaceutical companies worldwide, focusing on the development of drugs and therapies targeting ACC.

Introduction to Adenoid Cystic Carcinoma (ACC)

Adenoid cystic carcinoma (ACC) is a rare type of cancer that arises from the epithelial cells of secretory glands. The reported incidence of ACC is 4.5 cases per 100,000 population. It is characterized by slow-growing, infiltrative tumor growth with a tendency for perineural invasion. ACC commonly affects the salivary glands, particularly the major and minor salivary glands in the head and neck region. However, it can also occur in other locations, including the lacrimal glands, breast, and trachea.

ACC is known for its unique histological features, including a characteristic cribriform pattern, solid areas, and tubular structures. It is often associated with a prolonged clinical course, with a high propensity for local recurrence and distant metastasis, particularly to the lungs.

Pathogenesis of Adenoid Cystic Carcinoma (ACC)

It has been observed that ACC is often associated with genetic changes that occur throughout life, rather than being present in the germline. In particular, alterations in the MYB and MYB1 genes have been identified in ACC tumors. These genetic changes lead to the overexpression of certain proteins that drive the growth and progression of ACC, making them potential therapeutic targets.

Moreover, studies have shown that the activation of the MYB gene through gene fusion with the NFIB gene or other fusion partners is a key genomic event in ACC. This activation stimulates the proliferation of ACC cells and regulates genes involved in cell cycle control, DNA replication and repair, and RNA processing. Consequently, the oncogene has emerged as a promising diagnostic marker and potential target for therapeutic interventions in ACC.

Analysis of potential targets for therapeutic development in Adenoid cystic carcinoma (ACC).Fig. 1 Related therapeutic targets of ACC. (Miller L. E., et al., 2020)

Targets of Adenoid Cystic Carcinoma (ACC) Therapy

  • NOTCH1 Signaling Pathway
    The NOTCH1 signaling pathway plays a critical role in cell proliferation and survival. Mutations in the NOTCH1 gene have been associated with a more aggressive disease course in ACC cases. Targeting the NOTCH1 pathway with monoclonal antibodies has demonstrated partial responses in preclinical models, although human trials have shown limited efficacy.
  • Tumor Microenvironment and Immune Checkpoint Targets
    Checkpoint inhibitors, such as PD-1 monoclonal antibodies, have shown limited success in ACC cases. The expression of PD-L2 in ACC tumors and its association with immune infiltrates suggest a potential role for PD-L2 inhibition as a therapeutic strategy.
  • Protein Arginine Methyltransferase 5 (PRMT5)
    Inhibition of PRMT5 has shown promising results in inhibiting the growth of ACC in preclinical models.
  • Estrogen Receptor (ER)
    Increased expression of the ER-beta subtype has been observed in ACC tumors. The role of estrogen receptor blockade as a therapeutic approach in ACC is still under investigation.
  • PI3K/PTEN/mTOR Pathway
    Recurrent mutations in the FGF/IGF/PI3K pathway have been identified in ACC tumors. Inhibitors targeting this pathway, such as everolimus and lenalidomide in combination with everolimus, have shown promising efficacy in terms of disease stabilization and tumor shrinkage.
  • CDK/Cell Cycle Pathway
    High expression of cyclin-dependent protein kinase 6 (CDK6) has been observed in ACC samples. Inhibitors targeting CDK6 have shown potential as therapeutic options in ACC.

Therapies of Adenoid Cystic Carcinoma (ACC)

Targeted Therapies

Targeted therapies aim to specifically inhibit or modulate the molecular targets involved in ACC pathogenesis. Examples include inhibitors of the NOTCH1 signaling pathway, ER blockers, PI3K/PTEN/mTOR pathway inhibitors, and CDK inhibitors.

Immunotherapies

Immunotherapies, such as immune checkpoint inhibitors, aim to enhance the body's immune response against ACC. However, the success of immune checkpoint inhibitors in ACC has been limited, and further research is needed to optimize their efficacy.

Our Services

Accurate and timely diagnosis is crucial in managing ACC. Our company provides advanced diagnostics services that utilize cutting-edge technologies and techniques.

Therapy Development Platforms

Animal Models of Adenoid Cystic Carcinoma (ACC)

Genetic Engineering Model Development
Our company offers genetic engineering model (GEM) development services for studying ACC. GEMs allow for the manipulation of specific genes and pathways to better understand the role they play in tumor initiation, progression, and response to therapy.
Optional Models
  • MYB-Activated Model
  • MYB-NFIB Mouse Model
Xenograft Model Development
Patient-derived orthotopic xenograft (PDOX) models have emerged as a valuable tool in cancer research, as they faithfully recapitulate the characteristics of human tumors and their microenvironment. Our company specializes in the development of PDOX models for ACC, which have been shown to maintain high fidelity to human tumors and exhibit key features of the disease.
Optional Models
  • Ultrasound (US) -guided PDOX model
Optional Species Mouse, Rat, Non-human primates, Others

Furthermore, we offer a wide range of personalized animal models tailored to meet various requirements. If you are interested in our services, please do not hesitate to contact us for further information and details regarding pricing and related services.

Reference

  • Miller L. E., et al. "A contemporary review of molecular therapeutic targets for adenoid cystic carcinoma." Cancers 14.4 (2022): 992.

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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