Epithelial ovarian cancer (EOC) remains among the most lethal gynecological neoplasms, with a propensity for metastasis and insidious symptom presentation, and it predominantly afflicts postmenopausal females. Protheragen offers a wide array of services designed to support the entire EOC diagnostics and therapeutics development pipeline. From early-stage discovery to preclinical research, we provide end-to-end solutions that streamline the drug development process and accelerate the introduction of new therapeutics to the market.
Overview of Epithelial Ovarian Cancer (EOC)
Epithelial ovarian carcinoma (EOC) remains the predominant variant of ovarian cancer, distinguished by its common presentation at advanced stages, thus conferring an invariably unfavorable prognosis and an elevated mortality burden. The heterogeneity within the EOC umbrella is formally acknowledged; the separate histological types exhibit differentiating molecular and histopathological signatures, each of which modulates therapeutic sensitivity and prognostic trajectory. The predominant entity, high-grade serous carcinoma of the ovary (HGSOC), displays aggressive biology and is frequently linked with deleterious variants of the BRCA1 and BRCA2 loci, both of which play pivotal roles in the homologous recombination DNA repair pathway. Beyond HGSOC, the EOC continuum incorporates endometrioid, clear cell, mucinous, and low-grade serous carcinomas, each characterized by distinct patterns of chemoresistance and by varying levels of sensitivity to standard cytotoxic agents.
Fig.1 Evaluation and therapeutics of epithelial ovarian cancer. (Kuroki L.,
et al., 2020)
Diagnostics Development for Epithelial Ovarian Cancer (EOC)
Genomic Screening and Liquid Biopsies
Genomic screening and liquid biopsies are emerging as promising tools for early detection and monitoring of EOC. These methods involve analyzing circulating tumor DNA (ctDNA) in blood samples to identify specific genetic mutations associated with EPC. For instance, the detection of BRCA1/2 mutations and homologous recombination deficiency (HRD) can help in the early identification of patients who may benefit from targeted therapies such as PARP inhibitors.
Biomarker Identification
The identification of biomarkers is crucial for the early diagnosis and monitoring of EOC. CA125 is a well-established biomarker, but its sensitivity and specificity are limited. Newer biomarkers, such as human epididymis protein 4 (HE4), have shown improved diagnostic accuracy when combined with CA125. The Risk of Ovarian Cancer Algorithm (ROCA) uses serial measurements of CA125 to predict the risk of ovarian cancer, offering a more personalized approach to screening.
Therapeutics Development for Epithelial Ovarian Cancer (EOC)
- Targeted Therapies
Targeted therapies have revolutionized the therapeutic landscape for EOC. Anti-angiogenic agents like bevacizumab have shown significant benefits in improving PFS and OS when added to first-line chemotherapy and used as maintenance therapy. PARP inhibitors, such as olaparib, niraparib, and rucaparib, have demonstrated remarkable efficacy in maintenance therapy for patients with BRCA mutations or HRD. These agents exploit the DNA repair deficiencies in cancer cells, leading to enhanced cell death.
- Immunotherapy
Immunotherapy is an emerging field in EOC therapy, with checkpoint inhibitors showing promise in combination with other targeted agents. For instance, the combination of nivolumab and ipilimumab has demonstrated a response rate of up to 31% in patients with platinum-sensitive recurrent EOC. Additionally, the development of CAR-T cell therapies targeting specific antigens overexpressed in ovarian cancer cells is an area of active research.
- Antibody-Drug Conjugates (ADCs)
ADCs, such as mirvetuximab soravtansine, are being developed to target specific antigens overexpressed in ovarian cancer cells. These agents combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to therapeutics. Early clinical trials have shown promising results, with significant response rates in patients with platinum-resistant disease.
Table 1. Therapeutics of Epithelial Ovarian Cancer (EOC). (Kuroki L., et al., 2020)
| Drug |
Time of approval |
Agency |
Indications |
BRCA status |
Clinical setting |
Dosing |
| Olaparib |
Dec-18 |
FDA |
Advanced EOC, post CR/PR to platinum-based chemotherapy |
g/sBRCA |
First line maintenance |
300 mg BID |
| Aug-17 |
Advanced EOC
Platinum sensitive recurrent OC, post CR/PR |
gBRCA |
Monotherapy, fourth line |
| Feb-18 |
EMA |
Platinum sensitive recurrent HGOC, post CR/PR |
- |
Maintenance |
| Rucaparib |
Dec-16 |
FDA |
Advanced OC |
g/sBRCA |
Monotherapy, third line |
600 mg BID |
| Apr-18 |
Platinum sensitive recurrent OC, post CR/PR |
- |
Maintenance |
| May-18 |
EMA |
Platinum-sensitive recurrent or progressive HGOC |
g/sBRCA |
Monotherapy, third line |
| Jan-19 |
Platinum sensitive recurrent OC, post CR/PR |
- |
Maintenance |
- |
| Niraparib |
Mar-17 |
FDA |
Platinum sensitive recurrent OC, post CR/PR |
- |
Maintenance |
300 mg QD |
| Sep-17 |
EMA |
Platinum sensitive recurrent HGSOC, post CR/PR |
- |
Maintenance |
BID=twice daily;
BRCA=breast cancer susceptibility gene;
CR/PR=complete response or partial response;
EMA=European Medicines Agency;
FDA=Food and Drug Administration;
g/sBRCA=germline and/or somatic BRCA1/2 mutation;
HGOC=high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer;
HGSOC=high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer;
OC=epithelial ovarian, fallopian tube, or primary peritoneal cancer;
QD=once daily.
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 services for the development of diagnostics and therapeutics for EOC. Our services encompass the full spectrum of preclinical research, from biomarker identification and validation to the development of targeted therapies and immunotherapies. We utilize state-of-the-art technologies, including next-generation sequencing (NGS), proteomics, and advanced imaging techniques, to provide effective solutions for EOC therapeutics.
Disease Models
- Serous Ovarian Cancer Cell Line Models : OVCAR-3, SKOV3, HeyA8
- Clear Cell, Endometrioid, and Mucinous Ovarian Cancer Cell Line Models : ES-2, EFO-27, OVISE, and OVTOKO
- Mouse and Rat Ovarian Cancer Cell Lines: ID8, IG10, and IF5
- Xenograft Animal Models
Protheragen's preclinical research services are designed to accelerate the development of novel diagnostics and therapeutics for EOC. Our team of experts conducts rigorous preclinical studies using advanced models and techniques to evaluate the efficacy and safety of new agents. We offer a range of services, including in vitro and in vivo studies, pharmacokinetics and pharmacodynamics assessments, and biomarker discovery and validation. If you are interested in our services, please feel free to contact us.
References
- Kuroki, Lindsay, and Saketh R. Guntupalli. "Treatment of epithelial ovarian cancer." Bmj 371 (2020).
- Lheureux, Stephanie, et al. "Epithelial ovarian cancer." The Lancet 393.10177 (2019): 1240-1253.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
