Ovarian Granulosa Cell Tumor (OGCT), a genuinely uncommon malignancy, arises from ovarian granulosa cells—those that secrete estrogen during the maturation of ovarian follicles. Protheragen is at the forefront of OGCT diagnostics and therapeutics development, offering a comprehensive suite of services designed to accelerate the discovery and validation of novel biomarkers and therapeutic targets.
Overview of Ovarian Granulosa Cell Tumor (OGCT)
Ovarian granulosa cell tumors represent a small fraction—between two and five percent—of all ovarian tumors. What sets them apart clinically is the handsome time they take before making themselves known and the reasonable outlook that genuinely allows for effective intervention when spotted early. Recurrences, however, typically defy radical cure, and the handling of relapsing OGCT remains a daunting obstacle for practitioners. Most of the tumors show the adult pattern, presenting most commonly in women aged 50 to 55—we see the median sliding very few years in either direction. Those of the juvenile type, confined to girls before menstruation and women aged under thirty, occupy the rarer end of the spectrum.
Fig.1 Differential gene expression analysis comparing primary with recurrent adult-type granulosa cell tumors (aGCTs) identified a total of 31 DEGs, including genes involved in ovarian hormone signaling. (Khlebus E.,
et al., 2023)
Pathogenesis of Ovarian Granulosa Cell Tumor (OGCT)
The development of ovarian granulosa cell tumors (OGCTs) stems from several overlapping mechanisms that encompass alterations at both the genetic and systemic hormone levels. Central to the neoplasm’s molecular profile is the FOXL2 c.C402G (p.Cys134Trp) mutation, observed in the vast majority of primary OGCTs, and believed to act as an early driving alteration. A subset of tumors also harbors TERT C228T promoter mutations and inactivating KMT2D mutations; these genetic lesions tend to cluster in recurrent lesions, highlighting their potential contribution to therapy-resistant disease. On the endocrine front, OGCTs frequently secrete ovarian estrogen, an autocrine and/or paracrine mitogen that very likely amplifies the neoplastic growth signature. Recent studies underscore the importance of the tumor microenvironment, with the composition and functional status of infiltrating immune and stromal cell types shaping tumor aggressiveness and the risk of subsequent relapse.
Diagnostics Development for Ovarian Granulosa Cell Tumor (OGCT)
- Genomic Profiling
Next-generation sequencing (NGS) and RNA sequencing (RNA-seq) are used to identify specific genetic mutations and gene expression profiles associated with OGCTs. These techniques help in understanding the molecular basis of the disease and identifying potential biomarkers for early detection and prognosis.
- Functional Assays
Functional assays, such as cell proliferation and apoptosis assays, are used to study the effects of potential diagnostic markers on OGCT cells. These assays provide insights into the biological behavior of the tumor and help in validating the diagnostic potential of specific markers.
- Imaging Techniques
Advanced imaging techniques, such as MRI and CT scans, are used to visualize the tumor and assess its size and location. These imaging modalities are crucial for accurate diagnosis and staging of Ovarian Granulosa Cell Tumors (OGCTs).
Therapeutics Development for Ovarian Granulosa Cell Tumor (OGCT)
- Chemotherapy: Combination chemotherapy regimens, such as BEP (bleomycin, etoposide, and cisplatin) and paclitaxel/carboplatin, are commonly used for treating advanced or recurrent OGCTs. These regimens have shown efficacy in controlling tumor growth and improving survival rates.
- Hormonal Therapy: Given the hormonal nature of these tumors, aromatase inhibitors and other hormonal therapies are being explored for their potential benefits. These therapies aim to modulate estrogen levels and inhibit tumor growth.
- Targeted Therapy: Targeted therapies aimed at specific genetic mutations, such as FOXL2 and TERT, are being investigated. These therapies are designed to specifically target the molecular abnormalities driving tumor growth and progression.
- Immunotherapy: Immunotherapeutic approaches, including immune checkpoint inhibitors and other immunomodulatory agents, are being considered for OGCTs. These therapies aim to enhance the immune system's ability to recognize and attack tumor cells.
Table 1. Details of relapse and second-line therapy. (Khosla D., et al., 2014)
| Patient |
Stage |
First-line therapy |
EFS (months) since first line therapy |
Site of recurrence |
Therapy at relapse or progression (second-line therapy) |
Response to 2nd line at last follow-up |
Status |
EFS since 2nd line therapy (months) |
| 1 |
IIA |
FU only |
98.4 |
Pelvic recurrence |
Debulking surgery followed by CCT with 4 cycles of BEP, followed by pelvic RT |
SD |
Alive with disease |
26.33 |
| 2 |
IC |
Adjuvant RT |
96.23 |
Para-aortic and mediastinal nodes |
CCT with 4 cycles of BEP followed by RT to mediastinal nodes on progression |
PR |
Alive with disease |
18.87 |
| 3 |
IIIC |
CCT with 4 cycles of BEP |
66.33 |
Pelvic recurrence |
CCT with 8 cycles of paclitaxel and carboplatin |
CR |
NED |
13.23 |
| 4 |
IA |
FU only |
47.97 |
Pelvic recurrence |
Debulking surgery followed by 6 cycles of CCT with paclitaxel and carboplatin |
CR |
NED |
50.07 |
| 5 |
IIIC |
CCT with 6 cycles of paclitaxel and carboplatin |
42.63 |
Lung metastasis |
CCT with 4 cycles of BEP |
PR |
Alive with disease |
6.23 |
| 6 |
IIIC |
CCT with 4 cycles of BEP |
39.77 |
Pelvic and para-aortic recurrence |
CCT with 6 cycles of paclitaxel and carboplatin, followed by RT to the pelvis |
PR |
Died of disease (developed lung metastasis) |
10.17 |
| 7 |
IVA |
4 cycles of BEP |
37.3 |
Pelvic and abdominal recurrence, lung metastasis |
CCT with 3 cycles of paclitaxel and carboplatin |
PD |
Died of disease |
0 |
| 8 |
IC |
CCT with 4 cycles of BEP |
16.47 |
Pelvic, para-aortic, and mediastinal nodes, liver metastasis |
4 cycles of paclitaxel and carboplatin (progressive disease on chemotherapy) |
PD |
Died of disease |
0 |
BEP = Bleomycin, etoposide, and cisplatin, CCT = Combination chemotherapy, CR = Complete response, EFS = Event-free survival, FU = Follow-up, NED = No evidence of disease, PD = Progressive disease, PR = Partial response, RT = Radiotherapy, SD = Stable disease
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 Ovarian Granulosa Cell Tumor (OGCT). Our services encompass a wide range of preclinical research activities, from genomic profiling and functional assays to the development and validation of targeted therapies and immunotherapies. We leverage cutting-edge technologies and scientific expertise to provide tailored solutions for our clients, ensuring that their research and development efforts are supported by robust scientific data and innovative approaches.
Protheragen's diagnostics and therapeutics development services for OGCTs are defined by our unwavering dedication to scientific rigor, innovation, and client satisfaction. Our comprehensive suite of services is meticulously crafted to support every phase of preclinical research, spanning from the initial identification of therapeutic targets to the meticulous optimization of lead compounds. If you are interested in our services, please feel free to contact us.
References
- Khlebus, Eleonora, et al. "Comparative tumor microenvironment analysis of primary and recurrent ovarian granulosa cell tumors." Molecular Cancer Research 21.5 (2023): 483-494.
- Khosla, Divya, et al. "Ovarian granulosa cell tumor: clinical features, treatment, outcome, and prognostic factors." North American journal of medical sciences 6.3 (2014): 133.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
