Within the spectrum of ovarian tumours, approximately 8% are comprised of stromal and/or sex cord tumours, which originate from the connective tissue within the ovaries. These tumours are uniquely characterized by their ability to secrete hormones, thus contributing to hormonal imbalances commonly observed in patients. Among these, granulosa cell tumours (GCT) are the most prevalent, accounting for 5-10% of malignant ovarian cancers.
Adult GCT are characterised by a mutation in the FOXL2 gene (C134W), which is not present in the less common juvenile form (which represent 5% of GCT). These tumours closely mimic the morphological, biochemical and hormonal features of proliferating normal pre-ovulatory granulosa cells, including the production of estrogen and inhibin, with inhibin proving to be a valuable tumour marker. Despite their clinical significance, GCTs have received limited attention compared to other ovarian cancers, resulting in an incomplete understanding of their molecular pathogenesis.
A unique feature of GCT is their propensity for late recurrence, currently impossible to predict, along with an inability to determine a tumours behaviour leading to patient mortality. demise. Patients with recurrent or aggressive GCT have few therapeutic options, with approximately 80% succumbing to the disease. Treatments often rely on regimens designed for epithelial ovarian cancer and offer only limited benefit. Thus, there is a reliance on anecdotal reports to guide therapeutic decisions in the absence of robust evidence-based approaches.
In light of the relatively low incidence, limited specific therapeutic alternatives, and the tendency for late recurrence, patients with GCT have sought support from patient advocacy groups like the social media-based group “GCT Survivor Sisters”. Collaboratively, we are partnering with this group to guide our research efforts addressing critical questions that hold the potential to significantly impact patients and their families. This collaboration has unearthed a clear and consistent picture of key challenges of the disease, and are being addressed in five core themes of our research program, namely: 1) Social media and the patient experience; 2) Beyond FOXL2: decoding the genomic landscape of adult and juvenile GCT, 3) Elucidating the molecular pathogenesis of adult GCT, 4) Developing novel biomarker diagnostic assays, and 5) Combination therapy: A precision medicine approach for GCT.
In this symposium, we aim to shed light on some these crucial aspects of GCT research, ultimately driving us towards a better understanding of this understudied ovarian tumour, and, more importantly, improving the lives of those affected by it.