Precision oncology enables targeted therapies for gynecologic cancers, though acquired resistance remains a barrier.

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Frontiers in Medicine Published April 9, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that molecular reclassification enables targeted therapies, but acquired resistance remains a barrier requiring novel diagnostics and trials.

This systematic review evaluated the current landscape of precision oncology approaches for patients with gynecologic malignancies, specifically endometrial, ovarian, and cervical carcinomas. The study compared emerging diagnostic and therapeutic paradigms against historical management guided primarily by histomorphology and staging. No specific sample size or follow-up duration was reported for this review.

The review highlights that molecular reclassification has identified prognostically and therapeutically relevant subtypes. This reclassification has enabled the successful clinical translation of several targeted agents. Specifically, PARP inhibitors are established for homologous recombination deficient ovarian cancer. Immune checkpoint inhibitors are utilized for mismatch repair deficient or microsatellite instability-high endometrial and cervical cancers. Additionally, antibody-drug conjugates such as mirvetuximab soravtansine and tisotumab vedotin have shown successful translation in this setting.

Despite these advances, the review identifies that acquired resistance to these therapies remains a pivotal barrier. This resistance is driven by tumor evolution and heterogeneity. The study did not report specific data on adverse events, serious adverse events, discontinuations, or overall tolerability. Furthermore, no specific primary outcome metrics or statistical effect sizes were provided in the available evidence.

The practice relevance of this review underscores that the convergence of deep molecular phenotyping with targeted therapy is a cornerstone of modern care. Future directions require overcoming resistance through novel diagnostics, next-generation therapeutics, and innovative adaptive clinical trials. Equitable access to these evolving treatments is imperative to prevent widening health disparities.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

IntroductionThe clinical management of gynecologic malignancies endometrial (EC), ovarian (OC), and cervical (CC) carcinomas has been historically guided by histomorphology and staging. This paradigm fails to capture profound molecular heterogeneity, resulting in suboptimal outcomes. Precision oncology, through molecular taxonomy and biomarker-guided therapy, aims to address this gap.MethodsThis review synthesizes the current landscape of precision oncology in gynecologic cancers by analyzing established molecular classifications, the evidence for biomarker-guided therapies, mechanisms of therapeutic resistance, and emerging diagnostic and trial paradigms. The analysis is based on a critical evaluation of key literature and clinical trial data.ResultsMolecular reclassification, exemplified by The Cancer Genome Atlas (TCGA) for EC and OC, has identified prognostically and therapeutically relevant subtypes. This has enabled successful clinical translation of targeted agents: PARP inhibitors for homologous recombination deficient (HRD) ovarian cancer, immune checkpoint inhibitors for mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) endometrial and cervical cancers, and antibody-drug conjugates (ADCs) like mirvetuximab soravtansine and tisotumab vedotin. However, acquired resistance to these therapies, driven by tumor evolution and heterogeneity, remains a pivotal barrier.ConclusionThe convergence of deep molecular phenotyping with targeted therapy is a cornerstone of modern care. Future directions require overcoming resistance through novel diagnostics like liquid biopsy, next-generation therapeutics, and innovative adaptive clinical trials. Equitable access to these advances is imperative to prevent widening health disparities. The field is evolving towards a model of continuous molecular monitoring and adaptive therapy to improve outcomes.