Ovarian mucinous carcinoma (MOC), although comparatively uncommon, is a stand-alone category within epithelial ovarian cancer (EOC) that complicates clinical pathways due to its specific biological behavior. Protheragen offers a comprehensive suite of services for the preclinical development of MOC diagnostics and therapeutics. We provide a full-spectrum solution, from target identification and validation to lead optimization and preclinical testing.
Overview of Ovarian Mucinous Carcinoma (MOC)
Ovarian mucinous carcinoma (MOC) represents a rare, separate form of epithelial ovarian cancer, marked by voluminous, multilocular tumors filled with thick mucus. This subtype constitutes only about 3% to 5% of all epithelial ovarian malignancies. Despite its infrequency, MOC is frequently detected at a relatively early stage, with 65% to 80% of patients presenting with stage I disease. Yet, MOC that advances beyond that point—stages II to IV—carries a markedly unfavorable prognosis, with median survival usually constrained to 12 to 15 months. The tumors' distinctive biological characteristics include a limited responsiveness to standard first-line therapies, namely platinum-based regimens and PARP inhibitors. As a result, MOC demands tailored diagnostic and therapeutic strategies that extend beyond standard epithelial ovarian cancer protocols.
Fig.1 Representative images of ovarian mucinous carcinoma (OMC). (Hada T.,
et al., 2021)
Pathogenesis of Ovarian Mucinous Carcinoma (MOC)
The pathogenesis of MOC is multifactorial, involving genetic mutations and molecular pathways that drive tumor development and progression. Genetic aberrations such as ERBB2 (HER2) amplification, BRAF mutations, and KRAS/NRAS mutations are frequently observed in MOC. These genetic events contribute to the dysregulation of key signaling pathways, including the PI3K/AKT/mTOR pathway and the RAS/RAF pathway. Additionally, the overexpression of mucins (e.g., MUC1, MUC2, MUC5AC) plays a significant role in tumor progression and chemoresistance. Mucins form protective barriers that block the accessibility of therapeutic drugs and contribute to the invasive and metastatic potential of MOC cells.
Diagnostics Development for Ovarian Mucinous Carcinoma (MOC)
Immunohistochemistry (IHC)
IHC is a crucial diagnostic tool for MOC, enabling the detection of specific biomarkers such as HER2, estrogen receptor (ER), CK7, CK20, CDX2, and PAX8. HER2 amplification is a significant marker, with strong concordance between IHC and copy number analysis. ER positivity is observed in a subset of MOC cases, which may influence therapeutic decisions. For example, a study by Gorringe et al. (2020) reported that 10.6% of MOC cases were ER-positive, suggesting a potential role for hormonal therapy.
Genomic Sequencing
Next-generation sequencing (NGS) is employed to identify genetic mutations and amplifications that can inform targeted therapy. Whole exome sequencing (WES) and targeted sequencing panels are used to detect mutations in genes such as KRAS, NRAS, BRAF, TP53, PIK3CA, and PTEN. Comprehensive molecular profiling helps identify potential therapeutic targets. For instance, high-level ERBB2 amplifications and BRAF mutations are detected in a significant proportion of MOC cases, suggesting opportunities for targeted therapies.
Molecular Profiling
Molecular profiling involves the comprehensive analysis of genetic and molecular markers to understand the tumor's biology and identify potential therapeutic targets. This approach helps in the development of personalized therapeutic strategies for ovarian mucinous carcinoma (MOC) cases. For example, the detection of high-level ERBB2 amplifications and BRAF mutations can guide the use of targeted therapies such as anti-HER2 monoclonal antibodies and BRAF inhibitors.
Therapeutics Development for Ovarian Mucinous Carcinoma (MOC)
Several targeted therapies are being explored for MOC based on identified genetic aberrations. These include:
- HER2-Targeted Therapies: Anti-HER2 monoclonal antibodies (e.g., trastuzumab) and antibody-drug conjugates (e.g., T-DM1) for cases with ERBB2 amplification.
- BRAF Inhibitors: Targeting BRAF mutations, especially in combination with MEK inhibitors.
- PI3K/AKT/mTOR Pathway Inhibitors: For cases with PIK3CA mutations or PTEN inactivation.
- CDK4/6 Inhibitors: For cases with CDKN2A inactivation.
Table 1. Mucins and targeted therapy for ovarian cancer in clinical trials. (Wang Y., et al., 2023)
| Therapeutic agents (molecular target) |
Types of cancers eligible |
Total Patient |
Pathological types |
Key findings |
Year of Publication |
Authors |
Type of Study |
| Abagovomab (MUC16) |
Maintenance therapy of patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer |
888 |
Serous-726
Endometrioid -57
Mucinous-9
Other-91 |
No improvement in RFS or OS was observed. |
2013 |
(Sabbatini et al., 2013) |
Phase III |
| Oregovomab (MUC16) |
Maintenance therapy of patients with stage III or IV ovarian cancer |
145 |
Serous-89
Endometrioid-14
Other-42 |
Prolonged time to relapse, 13.2 months for the oregovomab group in the successful front-line therapy population. |
2004 |
(Berek et al., 2004) |
Phase III |
| Cvac (MUC1) |
Therapeutics in stage III or IV epithelial ovarian cancer patients who obtained a complete response to standard first (CR1) or second-line chemotherapy (CR2) |
63 |
N/R |
Improvement in PFS in 20 patients in CR2. |
2014 |
(Gray et al., 2014) |
Phase II |
| Gatipotuzumab (MUC1) |
Maintenance therapy of patients with recurrent epithelial primary ovarian, fallopian tube, or primary peritoneal cancer |
216 |
N/R |
No improvement in PFS or OS observed. |
2022 |
(Ledermann et al., 2022) |
Phase II |
| Cvac (MUC1) |
Therapeutics in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer |
28 |
Serous-22
Endometrioid-1
Endometrioid and clear cell-1
Other-2 |
Four patients showed CA125 response or stabilization (2 patients with major responses, 1 minor response, 1 stabilization). |
2014 |
(Mitchell et al., 2014) |
Phase II |
| Oregovomab (MUC16) |
Therapeutics of advanced ovarian cancer |
40 |
Serous-31
Mucinous-2
Other-7 |
33 patients achieved CR to surgery-carboplatin-paclitaxel-oregovomab. |
2009 |
(Braly et al., 2009) |
Phase II |
| Oregovomab (MUC16) |
Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer |
97 |
Mucinous-2
Serous-86
Endometrioid--6
Clear cell-2
Other-1 |
Significant improvement in PFS and OS.
Prolonged PFS 29.6 months for the oregovomab group.
OS has not yet been reached. |
2020 |
(Brewer et al., 2020) |
Phase II |
| DMUC5754A (ADC-MUC16) |
Therapeutics in patients with platinum-resistant recurrent ovarian cancer |
66 |
N/R |
Two patients had unconfirmed PR.
Six patients had SD lasting >6 months. |
2016 |
(Liu et al., 2016) |
Phase I |
| Gatipotuzumab (MUC1) |
Therapeutics of advanced ovarian carcinomas |
20 |
N/R |
The ORR was 40%.
5% patients achieve CR and 35% SD. |
2016 |
(Fiedler et al., 2016) |
Phase I |
| DMUC4064A (ADC-MUC16) |
Therapeutics in patients with platinum-resistant recurrent ovarian cancer |
65 |
N/R |
The clinical benefit rate was 42%.
27 patients had CR, PR, or SD lasting ≥6 months. |
2021 |
(Liu et al., 2021) |
Phase I |
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 for Ovarian Mucinous Carcinoma (MOC). Our services include advanced molecular profiling, immunohistochemistry, and next-generation sequencing to identify genetic mutations and biomarkers. We provide targeted therapies, hormonal therapy, and immunotherapy options based on the molecular profile of the tumor.
Protheragen's preclinical research services for MOC include the use of patient-derived models (e.g., cell lines, xenografts) to evaluate the efficacy of new targeted therapies. Our services involve comprehensive molecular profiling to identify potential therapeutic targets and guide the development of customized therapeutic strategies. If you are interested in our services, please feel free to contact us.
References
- Hada, Taira, et al. "Survival and biomarker analysis for ovarian mucinous carcinoma according to invasive patterns: retrospective analysis and review literature." Journal of Ovarian Research 14.1 (2021): 33.
- Wang, Yicong, Lifeng Liu, and Yongai Yu. "Mucins and mucinous ovarian carcinoma: Development, differential diagnosis, and treatment." Heliyon 9.8 (2023).
- Gorringe, Kylie L., et al. "Therapeutic options for mucinous ovarian carcinoma." Gynecologic oncology 156.3 (2020): 552-560.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
