Pulmonary Adenoid Cystic Carcinoma (PACC)

Pulmonary Adenoid Cystic Carcinoma (PACC) is an exceedingly rare and complex malignancy that originates from salivary gland-like tissue within the lung. Protheragen offers comprehensive services in both diagnostics and therapeutics development, drawing on our profound expertise in oncology and drug discovery.

Overview of Pulmonary Adenoid Cystic Carcinoma (PACC)

Pulmonary Adenoid Cystic Carcinoma (PACC) is a rare and intricate malignancy that arises from the submucosal glands of the trachea and bronchus. It is typified by its slow-growing nature, low-grade malignancy, and tendency for local invasion and distant metastasis. Given its nonspecific clinical symptoms, such as cough, hemoptysis, and shortness of breath, which closely resemble those of common respiratory diseases, PACC is often diagnosed at advanced stages. Histopathologically, PACC exhibits a range of growth patterns, including cribriform, tubular, and solid types, with the solid type being the most aggressive.

Fig.1 The diagnosis and therapeutic of PACC. (Chen Z., et al., 2023)

The pathogenesis of PACC is highly complex, encompassing a range of genetic and molecular alterations. A particularly significant genetic hallmark is the t (6;9) (q22-23; p23-24) translocation, which facilitates the fusion of the MYB gene with the NFIB gene. This fusion event triggers the overexpression of MYB and its downstream target genes. These overexpressed genes are instrumental in regulating key cellular processes such as the cell cycle, growth, apoptosis, and adhesion. Moreover, mutations within the Notch pathway, especially in the NOTCH1 gene, have been detected in certain PACC cases. These mutations play a crucial role in tumor progression and metastasis. Collectively, these genetic alterations lay the groundwork for the development of targeted therapeutic strategies. The goal of these strategies is to disrupt the oncogenic pathways that drive the development of PACC.

Diagnostics Development for Pulmonary Adenoid Cystic Carcinoma (PACC)

Immunohistochemical (IHC) Markers

The detection of high expression levels of specific IHC markers is instrumental in distinguishing PACC. Examples of markers found to be highly beneficial include CK7, CD117, P63, SMA, CK5/6, and S-100. These markers provide valuable insights into the cellular lineage and differentiation of the tumor, aiding in definitive diagnosis.

Genetic and Fusion Gene Detection

Advanced molecular techniques are increasingly being employed for PACC diagnosis. Notably, targeted RNA-sequencing has emerged as a powerful method for detecting specific fusion genes, such as MYB and MYBL1 fusions, which are characteristic of some adenoid cystic carcinomas. The presence of these fusions can serve as a highly specific diagnostic biomarker, potentially also guiding targeted therapeutic strategies.

Therapeutics Development for Pulmonary Adenoid Cystic Carcinoma (PACC)

• MYB Inhibitors: Targeted therapies aimed at inhibiting MYB and its downstream pathways are under investigation. Agents such as MYB peptidomimetics and ATR kinase inhibitors show promise in preclinical studies.
• C-Kit Inhibitors: Imatinib, a c-Kit inhibitor, has demonstrated efficacy in PACC patients with high c-Kit expression, highlighting the potential for targeted therapies in this subset of patients.
• Immune Checkpoint Inhibitors: Although monotherapy with PD-1/PD-L1 inhibitors has shown limited efficacy in PACC, combination therapies with other therapeutics are being explored to enhance antitumor effects.
• Cancer Vaccines: Vaccines targeting specific antigens, such as the MYB protein, are being developed to stimulate an immune response against PACC cells.

Table 1. The reported targeted therapy cases of PACC. (Chen Z., et al., 2023)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

At Protheragen, we are dedicated to offering a comprehensive one-stop service for both diagnostics and therapeutic development in the field of pulmonary adenoid cystic carcinoma (PACC). Our primary focus lies in the identification of novel biomarkers that can enable the accurate detection of PACC. In addition, we are committed to developing innovative preclinical therapeutic strategies that specifically target the unique molecular characteristics of this disease.

Diagnostics Development

• Karyotype Analysis Service
• Omics Analysis Service
• Biomarker Development Service
• Artificial Intelligence Service

Therapeutic Development

• Anticancer Peptide
• Gene Therapy
• Immunotherapy
• Monoclonal Antibody
• Small Molecule Drug
• Phytotherapy  
• Therapeutic Cancer Vaccine

Disease Models

• H292 Cell Lines
• Patient-Derived Lung Cancer Organoids (PDLCOs)
• Patient-Derived Xenograft (PDX) Models
• KRAS and TP53 Mutation Models
• Chemically Induced Models

Protheragen offers a robust suite of preclinical research services specifically designed for PACC. Our capabilities include comprehensive molecular profiling of PACC tumors, including analysis of MYB and MYBL1 fusion genes, to identify potential therapeutic targets. If you are interested in our services, please feel free to contact us.

References

• Chen, Zhixin, et al. "Pulmonary adenoid cystic carcinoma: molecular characteristics and literature review." Diagnostic Pathology 18.1 (2023): 65.
• Krifa, Marwa, et al. "Primary adenoid cystic carcinoma of the lung: a case report and literature review." Heliyon 7.2 (2021).

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.