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Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Colon Neuroendocrine Tumor

Colon Neuroendocrine Tumors (NETs) are a unique and difficult malignancy group requiring high-level level nuanced diagnostic and therapeutic approaches. At Protheragen, our extensive experience in biological research and drug development positions us at the forefront of advancing preclinical therapeutics for this nuanced disease.

Overview of Colon Neuroendocrine Tumor

Neuroendocrine tumors (NETs) of the colon are uncommon malignancies that arise from the neuroendocrine cells of the colon. These tumors are categorized into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs) following the 2019 WHO classification. Well-differentiated NETs tend to have a low growth potential and may be symptomless, often found incidentally during endoscopy or other diagnostic procedures. On the other hand, NECs are more aggressive and most the time associated with advanced disease. The prognosis for colon NETs is highly variable; however, well-differentiated colon NETs have a more positive prognosis than poorly differentiated NECs.

Pathological analysis: poorly differentiated neuroendocrine carcinoma of the colon.

Fig.1 Poorly differentiated neuroendocrine carcinoma of the colon. (Volante M., et al., 2021)

Pathogenesis of Colon Neuroendocrine Tumor

The development of colon neuroendocrine tumors stems from intricate systems of genetic and molecular changes. There are alterations in the Adenomatous Polyposis Coli (APC) gene, in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), and B-cell CLL/Lymphoma 9 (BCL9), which are located in both well-differentiated NETs to poorly differentiated NECs. Also, mutations of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) gene are known to occur in NECs. These changes may enhance, to some degree or another, the process where neuroendocrine cells become malignant tumors. Other possible causes include some genetic losses in chromosome 18q and the inactivation of suppressor genes on chromosome 11q.

Diagnostics Development for Colon Neuroendocrine Tumor

Biochemical Markers

Biochemical markers are essential for the diagnosis and management of colon neuroendocrine tumors. Urinary 5-hydroxyindole acetic acid (5-HIAA) and chromogranin A are commonly used markers. Elevated levels of 5-HIAA can indicate the presence of a carcinoid tumor, although its specificity is only about 88%. Chromogranin A is often elevated in patients with NETs and may indicate tumor burden. Other markers include neuron-specific enolase (NSE) and pancreatic polypeptide (PP).

Immunohistochemical Markers

Immunohistochemical markers are used to confirm the neuroendocrine phenotype of tumor cells. Synaptophysin and chromogranin A are commonly used markers that highlight the neuroendocrine nature of the tumor. Ki-67 is used to assess the proliferative index of the tumor cells, which is crucial for grading the tumor. Other markers include CD56 and CDX2, which can help differentiate between neuroendocrine and non-neuroendocrine components in mixed tumors.

Therapeutics Development for Colon Neuroendocrine Tumor

Chemotherapy: For metastatic disease, systemic chemotherapy plays a crucial role in reducing tumor burden and palliating symptoms, especially in cases of carcinoid syndrome. A common first-line chemotherapy regimen for high-grade metastatic neuroendocrine tumors of the colon and rectum involves a combination of cisplatin plus etoposide. This combination has demonstrated efficacy in managing aggressive forms of the disease.
High-Dose Induction Chemotherapy with Autologous Stem Cell Transplantation: In highly aggressive cases, such as mixed adenoneuroendocrine carcinoma with metastatic involvement, more intensive approaches like high-dose induction chemotherapy followed by autologous stem cell transplantation have been employed. This aggressive therapeutic modality aims for a more profound and durable remission, as demonstrated in a reported case where it led to complete and sustained remission.

Table 1. Therapeutics of Colon Neuroendocrine Tumor.

Therapeutics	Drug Name	Target	Description	Stage
Chemotherapy	Cisplatin, Etoposide	DNA, DNA topoisomerase II	Platinum-based chemotherapy regimens	Approved
Targeted Therapy	Octreotide, Lanreotide	SSTR	Management of symptoms related to hormone overproduction	Approved
Immunotherapy	PRRT (e.g., Lutetium-177 DOTATATE)	SSTR	Radiolabeled somatostatin analogues targeting somatostatin receptors	Approved

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

Protheragen offers comprehensive diagnostics and therapeutics development services tailored specifically for colon neuroendocrine tumors. Our services encompass the entire spectrum of preclinical research, from target identification and validation to drug discovery and preclinical studies.

Diagnostics Development

Therapeutic Development

Disease Models

Colonic NET Organoids
N-Methyl-N-Nitrosourea (MNU) Induced Models
N-Methyl-N-Nitrosoguanidine (MNNG) Induced Models
1,2-Dimethylhydrazine (DMH) Induced Models
Colon NET PDX Models

Protheragen's preclinical research services for colon neuroendocrine tumors are designed to accelerate the development of effective diagnostics and therapeutics. Our team of experts utilizes cutting-edge technologies to identify and validate molecular targets, develop novel imaging agents, and optimize therapeutic strategies. If you are interested in our services, please feel free to contact us.

References

Volante, Marco, et al. "Neuroendocrine neoplasms of the appendix, colon and rectum." Pathologica 113.1 (2021): 19.
Vanacker, Leen, et al. "Mixed adenoneuroendocrine carcinoma of the colon: molecular pathogenesis and treatment." Anticancer Research 34.10 (2014): 5517-5521.

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