As a type of neuroendocrine neoplasm (NENs), anal canal neuroendocrine carcinoma (ACNEC) stands out as an exceedingly aggressive and rare cancer. Protheragen recognizes that ANEC presents unique challenges and provides customized diagnostics and therapeutic development services to meet the specific needs of our clients.
Overview of Anal Canal Neuroendocrine Carcinoma (ANEC)
Anal canal neuroendocrine carcinoma (ANEC) is considered an uncommon and particularly aggressive kind of cancer due to the neuroendocrine anal canal cells from which it arises. This type of tumor usually develops at more advanced stages due to aggressive metastases. ANEC falls under neuroendocrine neoplasms (NENs) and is subclassified into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). ANECs typically fall into the latter category, exhibiting significant cytological atypia and high mitotic rates.
Fig.1 A case study of histopathological analysis of anal canal neuroendocrine carcinoma. (Morita R.,
et al., 2024)
Pathogenesis of Anal Canal Neuroendocrine Carcinoma (ANEC)
The pathogenesis of ANEC is incomplete, however, its development does involve several key factors. One such factor includes viral infections, most notably human papillomavirus (HPV) and human immunodeficiency virus (HIV). Specifically, high-risk subtypes of HPV, such as HPV-18, have been found in particular cases of ANEC, suggesting oncogenic potential due to the possible disruption of normal cellular homeostasis following integration into the host genome. Moreover, certain genetic changes in critical oncogenes and tumor suppressor genes are known to occur. For example, some cases have reported mutations in the PIK3CA gene, which could lead to dysregulated cell proliferation and enhanced survival signaling activity, constitutively activated cell growth and survival pathways.
Diagnostics Development for Anal Canal Neuroendocrine Carcinoma (ANEC)
Diagnosis of ANEC rests on a histopathological analysis alongside immunohistochemistry. In the case of ANECs, most show a population of small round or oval cells with scanty cytoplasm and a high nucleocytoplasmic ratio. These tumors tend to have high mitotic activity accompanied by a great deal of necrosis: features of aggression. Neuro-endocrine tumor characteristics require the application of some specific immunohistochemical assay. Of the most common are synaptophysin, chromogranin A, and CD56 which are classically found in ANECs. Furthermore, he can also express Thyroid transcription factor-1 (TTF-1) which helps in the distinction of primary ANEC from the metastatic small-cell carcinoma. These techniques serve to increase the precision with which one recognizes and classifies ANEC, helping with therapeutic development planning.
Therapeutics Development for Anal Canal Neuroendocrine Carcinoma (ANEC)
- Targeted Therapies
The development of molecular diagnostics has opened up possibilities for targeted approaches in ANEC therapies. TKIs like pemigatinib have shown promise in both preclinical and early-stage human trials, owing to specific genotypic changes highlighted via cancer genome profiling. These directed therapies improve therapeutic precision by reducing off-target interactions and, thus, enhancing therapeutic outcomes.
- Immunotherapy
Therapeutic approaches utilizing the body's immune response is an upcoming advancement in treating ANEC. Though it is currently in the early stages of development for this particular type of tumor, the effectiveness of immunotherapeutic drugs on other neuroendocrine tumors indicates some level of benefit. Immune checkpoint inhibitors like PD-1 and PD-L1 are showing good results in preclinical testing for neuroendocrine neoplasms.
Table 1. Therapeutics of anal canal neuroendocrine carcinoma (ANEC).
| Drug Name |
Target |
Description |
Stage |
| Cisplatin |
Tumor cells |
Often used in combination with etoposide for first-line treatment of poorly differentiated high-grade anal canal NEC. |
Approved |
| Etoposide |
Tumor cells |
Combined with cisplatin or carboplatin as a first-line chemotherapy regimen for advanced or metastatic anal canal NEC. |
Approved |
| Carboplatin |
Tumor cells |
Used in combination with etoposide as an alternative to cisplatin for first-line therapy. |
Approved |
| Irinotecan |
Tumor cells |
An alternative to etoposide in combination with cisplatin or carboplatin for first-line treatment of poorly differentiated anal canal NEC. |
Approved |
| Octreotide |
Somatostatin receptors |
A somatostatin analog used as first-line therapy for well-differentiated neuroendocrine tumors (NETs) with somatostatin receptor expression. |
Approved |
| Lanreotide |
Somatostatin receptors |
Another somatostatin analog used as first-line therapy for well-differentiated NETs with somatostatin receptor expression. |
Approved |
| Everolimus |
mTOR pathway |
An mTOR inhibitor used as second-line therapy for advanced well-differentiated NETs after progression on somatostatin analogs. |
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's diagnostics and therapeutics development services exemplify the comprehensiveness of both scope and depth. We incorporate the latest histopathological and molecular diagnostics with sophisticated preclinical research activities. This multimodal approach offers synergetic methods guiding innovative and tailored therapeutic development strategies.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- Anal Canal Organoids
- DMAB (3,2'-Dimethyl-4-Aminobiphenyl) Induced Models
- MNU (N-Methyl-N-Nitrosourea) and MNNG (N-Methyl-N-Nitrosoguanidine) Induced Models
- Xenograft and Syngeneic Models
Protheragen's preclinical research services are designed to address the complexities of ANEC through a multifaceted approach. If you are interested in our services, please feel free to contact us.
Reference
- Morita, Ryuichi, et al. "A Case Report of Primary Neuroendocrine Carcinoma of the Anal Canal with Cancer Genome Profiling." Internal Medicine (2024): 4289-24.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
