Nut Midline Carcinoma (NMC)
Nut midline carcinoma (NMC) is a rare and aggressive cancer that primarily affects midline structures such as the head, neck, and mediastinum. Our company, a leader in the field of rare disease research and therapy development, offers comprehensive services aimed at accelerating the development of drugs and therapies for NMC.
Introduction to Nut Midline Carcinoma (NMC)
Nut midline carcinoma (NMC), also known as NUT carcinoma (NC), is a rare and aggressive form of cancer that predominantly affects midline structures. Fewer than 100 cases have been reported in the literature. It is characterized by the presence of a chromosomal rearrangement resulting in the fusion of the BRD4 and NUT genes. This fusion event leads to the production of a fusion protein, BRD4-NUT, which plays a critical role in the development and progression of NMC.
NMC is often diagnosed in children, adolescents, and young adults, and it is associated with poor prognosis due to its aggressive nature and resistance to conventional therapeutic modalities.
Pathogenesis of Nut Midline Carcinoma (NMC)
The exact cause of NMC is still under investigation. However, studies have shown that the fusion of the BRD4 and NUT genes is a key genetic event that drives the development of NMC. This fusion is thought to arise from chromosomal translocations, where specific segments of DNA from the BRD4 and NUT genes are rearranged and fused. The BRD4-NUT fusion protein that is produced as a result of this genetic alteration disrupts normal cellular processes, leading to uncontrolled cell growth and tumor formation.
Fig. 1 Schematic of NUTM1 fusions. (Anderson G., et al., 2021)Pathological Analysis of Nut Midline Carcinoma (NMC)
Pathological analysis plays a crucial role in the diagnosis and characterization of Nut Midline Carcinoma (NMC). Histopathological examination of NMC samples typically reveals a highly undifferentiated tumor with small round cells. Immunohistochemistry staining can further confirm the presence of the BRD4-NUT fusion protein. Molecular techniques such as fluorescent in situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR) are employed to detect the specific fusion event between the BRD4 and NUT genes.
Targeted Therapies of Nut Midline Carcinoma (NMC)
BRD4-NUT Fusion Protein
The fusion protein resulting from the BRD4-NUT genetic alteration serves as a potential target for therapy development. Inhibitors that specifically target the function or expression of the fusion protein are being investigated.
BET Proteins
BET inhibitors, which interfere with the binding of BET proteins to acetylated histones, have shown promising activity in preclinical studies. These inhibitors disrupt the transcriptional activity of the BRD4-NUT fusion protein, potentially inhibiting tumor growth.
HDAC Inhibitors
Histone deacetylase (HDAC) inhibitors have demonstrated the ability to induce differentiation and growth arrest of NMC cells. However, further research is needed to optimize their efficacy and minimize drug tolerance.
CDK9 and p300
Inhibitors targeting CDK9 and p300 have shown promise in preclinical studies. CDK9 inhibition induces cell death in NMC cells, while p300 inhibition disrupts the interaction between BRD4-NUT and p300, leading to decreased transcription and oncogene expression.
Our Services
Our company is at the forefront of diagnostics and therapeutic development for Nut midline carcinoma. We offer a range of services designed to provide one-stop solutions for global pharmaceutical companies.
Therapy Development Platforms
Animal Models of Nut Midline Carcinoma (NMC)
To assess the efficacy and safety of potential therapies, it is essential to have reliable animal models that mimic the characteristics of NMC. Our company specializes in the development of animal models for NMC, allowing for in-depth preclinical research to evaluate the effectiveness of various therapeutic approaches.
| Genetic Engineering Model Development | |
| In line with the stochastic nature of fusion gene formation in human NMC, our GEMM model incorporates syntenic control of the resultant Brd4-Nutm1 fusion gene. This allows for the accurate representation of the genetic events leading to NC development. By leveraging the intrinsic low frequency of cre-lox-mediated interchromosome translocation, our GEMM model faithfully recapitulates the spontaneous occurrence of fusion genes, resembling the natural progression of NMC in humans. | |
| 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
- Kaplan H. G., et al. "Prolonged Survival of NUT Midline Carcinoma and Current Approaches to Treatment." The oncologist 28.9 (2023): 765-770.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.