Comprehensive molecular testing has become essential for personalized ovarian cancer treatment, with institutions increasingly adopting next-generation sequencing earlier in the disease course to optimize therapeutic strategies and clinical trial enrollment opportunities.
Current Biomarker Testing Framework
At diagnosis, comprehensive biomarker testing prioritizes BRCA1/2 germline and somatic testing, along with homologous recombination deficiency (HRD) and HER2 status assessment. In the recurrent setting, folate receptor alpha expression and additional markers including NTRK and RET fusions are reassessed to determine therapy eligibility.
The strategic shift toward upfront next-generation sequencing allows institutions to identify actionable targets sooner, enhancing future treatment flexibility and ensuring patients remain candidates for emerging therapies. Although certain targeted therapies are not yet FDA-approved for first-line use, early biomarker data enables better long-term treatment planning.
Expanding Beyond Traditional Markers
Several important biomarkers now guide ovarian cancer treatment beyond BRCA and HRD testing. Tumor-agnostic biomarkers include microsatellite instability (MSI)/mismatch repair deficiency and tumor mutational burden (TMB), which predict response to immunotherapy.
HER2 testing gained significant clinical relevance following the April 2024 FDA approval of trastuzumab deruxtecan for patients with 3+ expression, while the National Comprehensive Cancer Network recommends testing for 2+ expression as well.
Emerging Predictive Biomarkers
Diagnostic and predictive biomarkers are expanding treatment options across ovarian cancer subtypes. p53 testing distinguishes high-grade from low-grade serous ovarian cancer, while KRAS is expected to become an integrated biomarker for upcoming MEK/FAK inhibitor combination therapy in low-grade serous ovarian cancer.
CCNE1 amplification represents another promising biomarker, as it is mutually exclusive with BRCA mutations and associated with platinum resistance. Targeted therapies for CCNE1-amplified tumors are currently in development.
Clinical Implementation Strategies
There is growing interest in whether biomarkers like folate receptor alpha expression change over time, with some practitioners rechecking them in the recurrent setting to widen treatment or trial options. This approach reflects the evolving understanding of tumor biology and the potential for biomarker expression to shift during disease progression.
The field continues to advance through collaborative research networks, including the GOG Foundation and ENGOT, which are developing biomarker-directed treatments for gynecologic cancers. These efforts are expected to further refine personalized treatment approaches and expand therapeutic options for ovarian cancer patients.
