RNAi Therapy for Non-Genetic Ovarian Cancer
RNAi therapy is not currently recommended for non-genetic (BRCA wild-type) ovarian cancer in clinical practice, as it remains an investigational approach without established efficacy data or regulatory approval for this indication.
Current Treatment Standards for Non-Genetic Ovarian Cancer
The established treatment paradigm for BRCA wild-type ovarian cancer does not include RNAi therapeutics:
First-line therapy consists of platinum-based chemotherapy (carboplatin AUC 5-6 with paclitaxel 175 mg/m²) combined with bevacizumab 15 mg/kg every 3 weeks for six cycles, followed by bevacizumab maintenance 1
Maintenance options for BRCA wild-type patients after first-line platinum-based chemotherapy include niraparib (FDA-approved) or bevacizumab plus olaparib for those with genomic instability 2
Platinum-resistant recurrent disease is treated with sequential single-agent non-platinum chemotherapy (paclitaxel, pegylated liposomal doxorubicin, topotecan, or gemcitabine) combined with bevacizumab, focusing on quality of life and symptom control 3
RNAi as an Investigational Approach
While RNAi shows promise in preclinical studies, it has not translated to clinical use:
Preclinical evidence demonstrates that siRNA can target key oncogenic pathways in ovarian cancer cells, including ErbB3/NRG1 autocrine loops and DNA repair mechanisms like PARP1 4, 5
Research applications have successfully used RNAi screening to identify therapeutic targets and chemotherapy sensitizers, such as CHK1 and ATR inhibitors that potentiate cisplatin response 6
Delivery challenges remain the primary barrier, including RNA degradation, off-target effects, and immune responses, though nano-based delivery platforms are under development 4, 7
Theranostic approaches combining siRNA delivery with monitoring capabilities have shown promise in xenograft models but remain experimental 8
Critical Distinction: PARP Inhibitors Are Not RNAi Therapy
A common point of confusion must be clarified:
PARP inhibitors (olaparib, niraparib, rucaparib) work through small molecule inhibition of DNA repair enzymes, not through RNA interference mechanisms 2, 9
These agents have FDA approval and established efficacy in both BRCA-mutated and certain BRCA wild-type populations with homologous recombination deficiency 2
Clinical Recommendation
For non-genetic ovarian cancer, adhere to guideline-based therapies: platinum-based chemotherapy with bevacizumab for first-line treatment, followed by appropriate maintenance therapy based on homologous recombination deficiency status 2, 1. RNAi therapeutics should only be considered within the context of clinical trials, as no RNAi-based therapy has demonstrated clinical benefit or received regulatory approval for ovarian cancer treatment 4, 7.