Ovarian Serous Adenocarcinoma

Despite these advances, major challenges persist, including intratumoural heterogeneity and the poor diversity of genomic datasets. Artificial Intelligence (AI) technology, Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing, neoantigen-guided immunotherapy and ovarian cancer vaccination indicate a promising future for genomics-guided interventions and support the integration of genomics within multi-omic approaches to improve HGSOC outcomes.

Of two patients with the HER2-ultralow phenotype, one was alive with no evidence of disease at 16 months follow-up. The results support the idea that HER2/neu overexpression is exceptionally rare in LGSOC; nevertheless, future trials are essential to fully characterize the spectrum of HER2/neu alterations in LGSOC and to determine definitively whether the rare cases with mutations or ultralow expression could represent a small subgroup that might benefit from specific targeted agents.

Trametinib monotherapy achieved a 39% DCR in patients lacking standard options, supporting further studies to confirm efficacy and identify predictive biomarkers for treatment response.

P2, N=162, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Dec 2026

Nevertheless, the case underscores the importance of comprehensive germline testing and highlights potential, yet underexplored, genetic interactions that may influence ovarian cancer risk. To our knowledge, this represents the first reported case of HGSOC in a patient harboring both variants, offering a hypothesis‑generating observation for future investigation.

P1, N=104, Completed, Royal Marsden NHS Foundation Trust | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Jun 2025 --> Oct 2025

The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a least one Lipinski rule of five violation.

Our findings provide new insights into the metabolic and immunological mechanisms underlying SOC, and highlight potential targets for therapeutic interventions.

Ovarian cancer stem cell markers (ZIP-4 and ALDH1A1) can be considered potential prognostic markers in ovarian cancer patients. Moreover, ZIP-4 and ALDH1A1 expressions are related to resistance to platinum-based chemotherapy, which leads to ovarian serous carcinoma progression. Clinical implications suggest that future therapeutic regimens targeting ZIP-4 and ALDH1A1 may help overcome platinum-based chemotherapy resistance and improve patients outcomes.

P2, N=104, Not yet recruiting, Qinglei Gao

The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.