Ovarian cancer (OC) is the deadliest form of gynaecological malignancy and, in particular the epithelial histologic subtype (EOC), are often diagnosed at an advanced stage3,4. More than 90% of primary OC are EOC: high-grade serous, low-grade serous (LGSC), mucinous, endometrioid, and clear cell carcinomas5. The remainder are very rare variants, including Sex Cord Stromal tumours (granulosa cell tumours, Sertoli-Leydig tumours), which can be endocrine responsive6. The national WEHI-Stafford Fox Rare Cancer Program (SFRCP) streamlines rare cancer research, including that of rare ovarian cancer variants.
Of 609 SFRCP accruals to date, 217 have OC. We perform NGS testing to guide therapeutic outcomes: ~Whole Genome Sequencing (WGS) on fresh tumour samples and Whole Exome Sequencing (WES) on FFPE samples, depending on tumor purity (TP). H&E sections undergo anatomical pathology review to confirm diagnosis and to estimate TP.
Choice of therapeutics relevant for OC depends on an accurate OC subtype diagnosis. PARP inhibitor (PARPi) therapy has been transformative, particularly for women with EOC or carcinosarcoma with a BRCA1/2 mutation in their germline and/or OC. We are exploring mechanisms of PARPi resistance and the use of novel DNA repair inhibitors. Other novel therapeutics in development will be discussed, including less toxic antibody drug conjugates; the concept of targeting specific molecular aberrations (eg for mucinous OC or LGSC); and our experience with stromal tumours.