Colorectal Signet Ring Cell Carcinoma (CSRCC) represents a particularly aggressive and challenging subtype of colorectal cancer, demanding specialized approaches in both diagnosis and therapeutic development. Protheragen provides a comprehensive suite of services specifically tailored to address the complexities of Colorectal Signet Ring Cell Carcinoma (CSRCC).
Overview of Colorectal Signet Ring Cell Carcinoma (CSRCC)
Colorectal Signet Ring Cell Carcinoma (CSRCC) is a rare and aggressive subtype of colorectal cancer (CRC), characterized by the presence of signet ring cells, which are tumor cells with a distinctive morphology featuring intracytoplasmic mucin and a displaced nucleus. This histological subtype accounts for approximately 1% of all colorectal cancers but is notable for its poor prognosis and frequent metastasis, particularly to the peritoneum. CSRCC often presents at an advanced stage, with patients typically being younger than those with conventional colorectal adenocarcinomas. The unique clinical and molecular features of CSRCC necessitate specialized diagnostic and therapeutic approaches.
Fig.1 Comparison of molecular features between signet ring cell carcinoma (SRCC) and adenocarcinoma (AC). (An Y.,
et al., 2021)
Pathogenesis of Colorectal Signet Ring Cell Carcinoma (CSRCC)
The pathogenesis of CSRCC involves a complex interplay of genetic and epigenetic alterations. Key molecular changes include mutations in TP53, ARID1A, APC, KRAS, and BRCA1, which disrupt normal cellular processes and contribute to tumor progression. Additionally, CSRCC frequently exhibits microsatellite instability (MSI), a condition characterized by defects in the DNA mismatch repair system, leading to an accumulation of genetic mutations. Loss of E-cadherin expression, encoded by the CDH1 gene, is also common, resulting in reduced cell-cell adhesion and facilitating tumor invasion. Epigenetic modifications, such as DNA methylation and histone changes, further contribute to the dysregulation of gene expression in CSRCC.
Diagnostics Development for Colorectal Signet Ring Cell Carcinoma (CSRCC)
Molecular Profiling
Molecular profiling using next-generation sequencing (NGS) and immunohistochemistry (IHC) is crucial for identifying specific genetic mutations and protein expression patterns in CSRCC. These techniques help in understanding the molecular characteristics of the tumor and identifying potential therapeutic targets. For example, NGS can detect MSI status and mutations in key oncogenes and tumor suppressor genes, while IHC can assess the expression of proteins such as E-cadherin and PD-L1.
Biomarker Identification
Research is ongoing to identify biomarkers that can aid in the early detection and diagnosis of CSRCC. Circulating tumor DNA (ctDNA) analysis is a promising approach, as it can detect specific mutations in the bloodstream, providing a non-invasive diagnostic tool. Additionally, the identification of tumor-specific proteins in blood or tissue samples can serve as diagnostic indicators.
Therapeutics Development for Colorectal Signet Ring Cell Carcinoma (CSRCC)
- Targeted Therapies
Targeted therapies aim to inhibit specific molecular pathways that are dysregulated in CSRCC. For instance, drugs targeting MSI-high tumors, such as immune checkpoint inhibitors (e.g., pembrolizumab), have shown promise in clinical trials. Other targeted therapies may focus on inhibiting oncogenic pathways involving KRAS, BRAF, or PI3K/AKT/mTOR signaling.
- Immunotherapy
Immunotherapies, including immune checkpoint inhibitors and CAR-T cell therapies, are being explored for their potential to enhance the immune system's ability to recognize and attack CSRCC cells. These therapies aim to modulate the immune response to improve therapeutic outcomes and reduce the risk of recurrence.
Table 1. Therapeutics of Colorectal Signet Ring Cell Carcinoma (CSRCC).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Fluorouracil |
DNA synthesis |
Beneficial in advanced stages, especially in stage III. |
Approved |
| Chemotherapy |
Irinotecan, Oxaliplatin |
DNA topoisomerase I, DNA synthesis |
Limited efficacy in CSRCC. |
Approved |
| Hyperthermic Intraperitoneal Chemotherapy (HIPEC) |
N/A |
N/A |
Proposed for selected patients with peritoneal metastasis. |
Approved |
| Targeted Therapy |
PARP inhibitors |
DNA repair |
Potential in BRCA1-mutated CSRCC. |
Preclinical |
| Targeted Therapy |
N/A |
RNF43, PIK3CA, ERBB2, BRAF |
Potential targets identified through molecular profiling. |
Preclinical |
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 understands that each client has unique needs and requirements. Our customized services are tailored to meet the specific demands of our clients, providing flexible and customized solutions for CSRCC diagnostics and therapeutics development.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
- Customized Diagnostics Development Service
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- HT-29 Cell Lines
- LS174T Cell Lines
- Patient-Derived Organoids
- ApcMin Mouse Models
- ApcΔ14 Mouse Models
- Chemical-Induced Models
Protheragen's diagnostics and therapeutics development services for CSRCC are characterized by our state-of-the-art technologies, rigorous scientific methodologies, and commitment to innovation. If you are interested in our services, please feel free to contact us.
References
- An, Yang, et al. "Clinicopathological and molecular characteristics of colorectal signet ring cell carcinoma: a review." Pathology and Oncology Research 27 (2021): 1609859.
- Nuytens, Frederiek, et al. "Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma." World Journal of Gastrointestinal Oncology 16.5 (2024): 2141.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
