bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–07–05
eleven papers selected by
Lara Paracchini, Humanitas Research
  1. Differences in overall survival for invasive epithelial ovarian cancer by race and ethnicity: results from the Ovarian Cancer Association Consortium.
  2. Understanding risk perception and risk-reducing decision-making for surgery among individuals with a genetic predisposition to epithelial ovarian cancer.
  3. Escaping the trap.
  4. Early detection of multiple cancers: the era of methylation-based liquid biopsy.
  5. Longitudinal methylated ctDNA increases predict immunotherapy progression across solid tumors.
  6. Multi-omics analysis in suspected hereditary breast and ovarian cancer cases reveals novel candidate susceptibility factors.
  7. Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.
  8. Liquid biopsy, multi-cancer early detection, and artificial intelligence: new frontiers in cancer screening from a technological and immunological perspective.
  9. CLIM-TIME links tumour genetics to spatial immune architecture.
  10. Breaking news from ESMO 2025: liquid biopsy novelties in gastrointestinal cancer.
  11. Germline CDK12 variants in aggressive prostate cancer.
  1. Br J Cancer. 2026 Jun 30.
    Differences in overall survival for invasive epithelial ovarian cancer by race and ethnicity: results from the Ovarian Cancer Association Consortium.
    AOCS Group
       BACKGROUND: Prior studies have examined survival in patients with epithelial ovarian cancer (EOC); however, few consider race and ethnicity, particularly disaggregating Asian and Native Hawaiian/Pacific Islander women.
    METHODS: We analysed data from 18 Ovarian Cancer Association Consortium studies, including women with EOC from Asian (n = 697), non-Hispanic Black (n = 267), Hispanic (n = 492), Native Hawaiian/Pacific Islander (n = 98) and non-Hispanic White (n = 12,998) racial and ethnic groups. We ran Cox proportional hazards models estimating overall survival by race and ethnicity, adjusting for age, stage, year of diagnosis, and histotype, with fully adjusted models accounting for body mass index, smoking, and postmenopausal hormone use. We also examined associations between hormone-related factors and family history and overall survival by race and ethnicity, testing for heterogeneity.
    RESULTS: Compared to non-Hispanic White women with EOC, Native Hawaiian/Pacific Islander and non-Hispanic Black women had poorer overall survival (Hazard Ratios, HR = 1.58, 95% CI = 1.16-2.16, and HR = 1.31, 95% CI = 1.12-1.54, respectively). The association was more pronounced for Native Hawaiian/Pacific Islander women with high-grade serous carcinoma (HR = 2.00, 95% CI = 1.37-2.92). There was no significant heterogeneity in the associations between epidemiological factors and survival by racial and ethnic groups (p ≥ 0.31).
    DISCUSSION: Native Hawaiian/Pacific Islander and non-Hispanic Black women with EOC had poorer survival, highlighting the need to address disparities in outcome.
    DOI:  https://doi.org/10.1038/s41416-026-03509-8
  2. J Genet Couns. 2026 Aug;35(4): e70225
    Understanding risk perception and risk-reducing decision-making for surgery among individuals with a genetic predisposition to epithelial ovarian cancer.
    Rebekah Kukurudz-Gorowski, Sylvia Horn, Pascal Lambert, Kim Serfas, Renée El-Gabalawy, Alon David Altman, Kirk James McManus, Jessica Nicole Hartley, Mark William Nachtigal.
      Genetic predisposition to hereditary breast and ovarian cancer and Lynch syndrome increases the risk of developing cancer, including epithelial ovarian cancer (EOC). Depending on the pathogenic variant, (e.g., BRCA1 or PMS2) the risk of developing EOC ranges from approximately 3%-60%. To reduce this risk, many individuals are offered risk-reducing salpingo-oophorectomy (RRSO), a procedure in which fallopian tubes and ovaries are removed. Some centers have dedicated programs that provide targeted care for individuals at risk of gynecologic cancers, such as the Hereditary Gynecology Clinic in Winnipeg, Manitoba. To better understand how individuals across a spectrum of risk values for developing EOC interpret their personal risk and make decisions regarding RRSO, we conducted a convergent mixed-methods study involving an online survey and virtual interview. Sixty-three surveys and twenty interviews were completed. Participants viewed objective risk information as a starting point, to which 'experiential knowledge' and perceived control were applied and integrated into their personal subjective risk assessment. Perceived risk was intertwined with cancer worry, and individuals made decisions regarding RRSO based on factors such as perceived risk, control, family planning, hormonal impacts, and recovery. Importantly, healthcare providers exerted both direct and indirect influences on the decision-making process.
    Keywords:  HBOC; Lynch syndrome; RRSO; decision‐making; epithelial ovarian cancer; risk perception
    DOI:  https://doi.org/10.1002/jgc4.70225
  3. Nat Rev Cancer. 2026 Jul 02.
    Escaping the trap.
    Daniela Senft.
      
    DOI:  https://doi.org/10.1038/s41568-026-00957-5
  4. Front Oncol. 2026 ;16 1850041
    Early detection of multiple cancers: the era of methylation-based liquid biopsy.
    Yajie Lin, Zekai Hu, Leyao Shuai, Zhaowei Tong, Hainv Gao, Junsheng Zhao.
      Liquid biopsy based on circulating cell-free DNA (cfDNA) methylation has become a leading non-invasive strategy for multi-cancer early detection (MCED). Aberrant DNA methylation arises at the early stage of tumorigenesis and displays cancer-type-specific signatures, enabling early capture of tumor-derived epigenetic signals. High-throughput sequencing, digital PCR and machine learning algorithms have greatly improved the sensitivity and specificity of methylation-based assays. Large-scale clinical trials including CCGA, PATHFINDER, THUNDER and GUIDE have validated that MCED tests achieve high specificity (>99%) and reliable accuracy for tissue of origin prediction. Integrating methylomics with fragmentomics further boosts early detection performance, especially for early-stage tumors with low ctDNA shedding. Nevertheless, clinical translation still faces notable hurdles, including technical standardization, biological confounding factors, high cost and the demand for large-scale prospective mortality endpoint validation. Future development will rely on multi-omics integration, optimized bioinformatic pipelines and standardized interventional trials to lower cancer-specific mortality. In summary, methylation liquid biopsy is poised to reshape cancer screening from single-organ late diagnosis to multi-cancer early intervention, offering profound prospects for precision oncology.
    Keywords:  DNA methylation; biomarker; circulating tumor DNA (ctDNA); liquid biopsy; multi-cancer early detection
    DOI:  https://doi.org/10.3389/fonc.2026.1850041
  5. J Liq Biopsy. 2026 Sep;13 100477
    Longitudinal methylated ctDNA increases predict immunotherapy progression across solid tumors.
    Muhammad Anees, Patrick L Wagner, Ashten Omstead, Erin Grayhack, Christopher Sherry, Lee D McDaniel, Matthew G Varga, Seyed Mohammad Hossein Hosseiny, William Laframboise, John Nakayama, Thomas Krivak, Benny Weksler, Neda Dadgar, Shurjeel Uddin Qazi, Nathan Bahary, David L Bartlett, David S Tsao, Ali H Zaidi.
      Timely identification of treatment failure during immune checkpoint blockade remains a critical unmet need in oncology. We evaluated a tissue-free, methylation-based circulating tumor DNA (ctDNA) assay applied serially across 142 patients with advanced solid tumors receiving immune checkpoint inhibitor monotherapy or chemo-immunotherapy in two independent prospective cohorts. Blood was collected pre-treatment, C2D1, and C3D1. Molecular progression, mPD, was defined as an increase in ctDNA while on therapy. mPD stratified progression-free and overall survival across both cohorts (PFS HR 5.8 95% CI 3.4-9.9; OS HR 4.1 95%CI 2.3-7.0). Notably, incorporating ctDNA at C2 identified more molecular rebounders, and mPD was significant for OS in RECIST 6-month BOR stable disease subgroup where imaging is least informative (HR 8.4, 95% CI 1.4 to 48.7). Monitoring with ctDNA continued to predict progression after C3 and identified progression with median lead time of 62 days. These findings confirm prior studies that have shown that ctDNA is predictive for immunotherapy response and furthermore demonstrate the utility of a clinically practical molecular progression rule across the multiple cancer types treated by immune checkpoint inhibitors.
    Keywords:  DNA methylation; Immune checkpoint inhibitors; Liquid biopsy; Northstar; Pan-cancer; Response monitoring; Tumor-naive assay; ctDNA
    DOI:  https://doi.org/10.1016/j.jlb.2026.100477
  6. NPJ Breast Cancer. 2026 Jun 30. pii: 87. [Epub ahead of print]12(1):
    Multi-omics analysis in suspected hereditary breast and ovarian cancer cases reveals novel candidate susceptibility factors.
    B Aldrige Allister, Winfried Hofmann, Jonathan L Lühmann, Björn Sander, Lena Wendeburg, Gunnar Schmidt, Bernd Auber, Susanne Morlot, Hannah Wallaschek, Nataliya di Donato, Brigitte Schlegelberger, Monika M Golas, Doris Steinemann.
      More than 80% of patients who meet clinical criteria for hereditary breast and ovarian cancer (HBOC) do not show pathogenic variants in BRCA1, BRCA2, and other diagnostically consented core genes. We hypothesized that variants in further DNA repair genes, cryptic genomic alterations, or polygenic factors may explain HBOC risk. We studied 134 patients with breast cancer and/or ovarian cancer by the use of whole genome sequencing (WGS), whole transcriptome sequencing (WTS), optical genome mapping (OGM), and mobile element analysis. We identified (likely) pathogenic variants in DNA repair genes in 18 patients, including several RECQ helicase and other DNA repair genes, an intragenic FANCM deletion, and six rare mobile element insertions (MEIs) in DNA repair genes. Incorporating PRS306 shifted estimated lifetime breast cancer risk by ≥5 percentage points in a subset of women (n = 75), including carriers of rare variants in DNA repair genes, resulting in both upward and downward risk estimation.
    DOI:  https://doi.org/10.1038/s41523-026-01003-1
  7. Clin Cancer Res. 2026 Jul 01.
    Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.
    Nurit Gal-Mark, Assaf Grunwald, Valid Gahramanov, Michal Hameiri-Grossman, Elena Shinderman-Maman, Dafna Gaash, Keren Shichrur, Jaques Mordoukh, Nino Oniashvili, Eva Chausky Barzakh, Aviv Sever, Shirah Amar, Shifra Ash, Yehudit Birger, Shai Izraeli, Yuval Ebenstein, Esther R Berko.
       PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma.
    EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles to a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBLs) that were reliably detectable in cfDNA. Marker robustness and specificity were validated using independent neuroblastoma methylation datasets and assessed against methylation profiles from other cancer types. We established neuroblastoma as a distinct methylation entity within the reference atlas by integrating a panel of 25 meNBLs, enabling quantitative estimation of tumor-derived cfDNA. Assay performance was evaluated across diagnostic, remission, relapse, and healthy control samples and compared with mutation- and copy number-based approaches.
    RESULTS: Neuroblastoma-derived cfDNA was consistently detected at diagnosis and relapse, but was absent in healthy controls and during confirmed remission. Methylation-based deconvolution demonstrated high specificity, with no detectable background signal in controls, and improved performance relative to copy number-based tumor fraction estimation. Longitudinal profiling enabled early molecular detection of relapse and reliable disease monitoring.
    CONCLUSIONS: We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients including those lacking trackable genomic alterations. This approach supports clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-26-0457
  8. Front Immunol. 2026 ;17 1854718
    Liquid biopsy, multi-cancer early detection, and artificial intelligence: new frontiers in cancer screening from a technological and immunological perspective.
    Dong Wu, Qing Yu, Qixiang Wu, Xiaoying Wang, Haojie Wei, Fengli Li, Guangli Li, Xiaowu Wang, Xiaojuan Wang.
      Early cancer detection remains a central challenge in oncology because many lethal tumors are diagnosed after curative opportunities have narrowed, whereas current organ-specific screening methods cover only a limited number of cancer types and may be constrained by invasiveness, cost, accessibility or stage-dependent sensitivity. Liquid biopsy, multi-cancer early detection (MCED) and artificial intelligence (AI) are rapidly reshaping this field, but their clinical implications require careful interpretation. This review critically evaluates major liquid-biopsy analytes, including circulating tumor DNA, cell-free DNA methylation and fragmentomics, circulating tumor cells, extracellular vesicles, non-coding RNAs, tumor-educated platelets and multi-omics signatures, with emphasis on intended use, clinical maturity, tissue-of-origin value and translational limitations. A distinctive feature of this review is the integration of tumor-derived signals with host-response and immunological readouts, including peripheral blood mononuclear cell-based monitoring, immune-cell-derived extracellular vesicles, exosomal immune-checkpoint molecules and inflammatory confounders, thereby framing liquid biopsy as both a cancer-detection tool and a window into tumor-immune interactions. We further discuss MCED as a clinical care pathway rather than an isolated blood test, highlighting the importance of positive and negative predictive values, cancer prevalence, diagnostic-resolution pathways, false-positive workup, overdiagnosis, mortality benefit, cost-effectiveness and equitable access. The role of AI is examined in relation to model development, multimodal fusion, tissue-of-origin prediction, calibration, interpretability, bias, generalizability and clinical implementation. Across these technologies, a key translational message is that technical detectability is not equivalent to clinical readiness. While selected assays have entered defined clinical or guideline-supported settings, many emerging biomarkers and AI-enabled models remain investigational or translational. Future progress will depend on standardized workflows, prospective validation in representative populations, evidence of clinical utility, regulatory and ethical oversight, and integration with established screening and diagnostic systems.
    Keywords:  artificial intelligence; clinical validation; early cancer detection; liquid biopsy; multi-cancer early detection; tumor immune interactions
    DOI:  https://doi.org/10.3389/fimmu.2026.1854718
  9. Nat Rev Cancer. 2026 Jun 29.
    CLIM-TIME links tumour genetics to spatial immune architecture.
    Weiwei Hu.
      
    DOI:  https://doi.org/10.1038/s41568-026-00956-6
  10. J Liq Biopsy. 2026 Jun;12 100466
    Breaking news from ESMO 2025: liquid biopsy novelties in gastrointestinal cancer.
    Serena Pillozzi, Giulia Petroni, Daniele Lavacchi, Daniele Rossini, Lorenzo Antonuzzo.
      Liquid biopsy (LB) has emerged as a minimally invasive approach to characterize tumor biology and support treatment decision-making across gastrointestinal (GI) malignancies. Advances in circulating biomarkers have expanded its potential clinical applications. While colorectal cancer appears closest to clinical implementation, with ctDNA increasingly integrated into adjuvant and metastatic decision-making, applications in other GI tumors remain largely exploratory. Emerging approaches, including cfDNA methylation profiling, multi-omic assays, and circulating protein or metabolite analyses, have shown promising early signals but require prospective validation. This review summarizes key LB findings presented at ESMO 2025, highlighting translational relevance, current limitations, and future directions for clinical integration.
    Keywords:  Circulating tumor DNA (ctDNA); Gastrointestinal cancers; Liquid biopsy; Minimal residual disease (MRD); Personalized medicine
    DOI:  https://doi.org/10.1016/j.jlb.2026.100466
  11. Cancer Discov. 2026 Jul 02.
    Germline CDK12 variants in aggressive prostate cancer.
    Sofie H Tolmeijer, Corinne Maurice-Dror, Shahneen Sandhu, Claire M de la Calle, Christian Kollmannsberger, Mohamed Adil, Catherine K Wang, Andrew J Murtha, Gráinne Donnellan, Nielka P van Erp, Niven Mehra, Michael S Hofman, Arun A Azad, Ian D Davis, Andries M Bergman, Wilbert Zwart, Kim van der Zande, Lesley Seymour, Peter C Black, Vahid Akbari, Lilian Cordova, Peter M Lansdorp, Steven Jm Jones, Peter S Nelson, Elena Castro, Kasmintan A Schrader, Gavin Ha, Heather H Cheng, Piet Ost, David Olmos, Kim N Chi, Colin C Pritchard, Alexander W Wyatt.
      CDK12 mutations occur in 2-7% of metastatic prostate cancers (mPCa) and are considered to be exclusively somatic. Here, we identified five patients with mPCa (ages 44-62) harboring germline CDK12 truncating variants among 4,535 tested (0.1%). All had CDK12-driven cancers defined by an additional somatic CDK12 variant and the CDK12-specific hallmark genomic instability signature characterized by hundreds of tandem duplications. Two patients had multiple independent CDK12-driven tumors with distinct secondary somatic CDK12 variants. Germline CDK12 truncating variants were enriched in mPCa compared to gnomAD V4.1.0 controls (n=807,162; odds ratio 11.4, 95% CI 3.6-27.8) and V2.1.1 non-cancer controls (n=134,187; odds ratio 29.6; 95% CI 6.8-28.6). Family history revealed multiple related individuals with prostate or ovarian cancer, and germline variant inheritance was confirmed in the two tested pedigrees. Our data suggest that germline CDK12 truncating variants are a rare driver of lethal mPCa.
    DOI:  https://doi.org/10.1158/2159-8290.CD-26-0084
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