bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–04–05
nine papers selected by
Lara Paracchini, Humanitas Research
  1. Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.
  2. Epigenetic regulation of cancer.
  3. Hereditary gynecological cancer management in women with Lynch syndrome: a survey across Europe.
  4. Integrating liquid biopsies and artificial intelligence for early cancer detection: A systematic review and meta-analysis.
  5. Natural menopause, menarche and breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers: a Mendelian randomization analysis.
  6. Utility of Circulating Tumor DNA-Based Liquid Biopsies in Patients with Cancer Receiving Immunotherapy.
  7. Single-cell and spatial profiling in cancer biology and clinical oncology.
  8. Measuring and defining screening benefit in a new era of cancer early detection.
  9. Clinical impact of clonal hematopoiesis on patients with solid tumors: a systematic review and meta-analysis.
  1. Nat Commun. 2026 Apr 01.
    Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.
    Tibor A Zwimpfer, Sian Fereday, Ahwan Pandey, Dinuka Ariyaratne, Madawa W Jayawardana, Laura Twomey, Céline M Laumont, Catherine J Kennedy, Adelyn Bolithon, Nicola S Meagher, Katy Milne, Phineas Hamilton, Jennifer Alsop, Antonis C Antoniou, George Au-Yeung, Matthias W Beckmann, Amy Berrington de Gonzalez, Christiani Bisinotto, Freya Blome, Clara Bodelon, Jessica Boros, Alison H Brand, Michael E Carney, Alicia Cazorla-Jiménez, Derek S Chiu, Elizabeth L Christie, Anita Chudecka-Głaz, Penny Coulson, Kara L Cushing-Haugen, Cezary Cybulski, Kathleen M Darcy, Cath David, Trent Davidson, Arif B Ekici, Esther Elishaev, Julius Emons, Tobias Engler, Rhonda Farrell, Anna Fischer, Montserrat García-Closas, Aleksandra Gentry-Maharaj, Prafull Ghatage, Rosalind Glasspool, Philipp Harter, Andreas D Hartkopf, Arndt Hartmann, Sebastian Heikaus, Brenda Y Hernandez, Anusha Hettiaratchi, Sabine Heublein, David G Huntsman, Mercedes Jimenez-Linan, Michael E Jones, Eunyoung Kang, Ewa Kaznowska, Tomasz Kluz, Felix K F Kommoss, Gottfried Konecny, Roy F P M Kruitwagen, Jessica Kwon, Diether Lambrechts, Cheng-Han Lee, Jenny Lester, Samuel C Y Leung, Yee Leung, Anna Linder, Jolanta Lissowska, Liselore Loverix, Jan Lubiński, Constantina Mateoiu, Iain A McNeish, Malak Moubarak, Gregg S Nelson, Nikilyn Nevins, Alexander B Olawaiye, Siel Olbrecht, Sandra Orsulic, Ana Osorio, Carmel M Quinn, Ganendra Raj Mohan, Isabelle Ray-Coquard, Cristina Rodríguez-Antona, Patricia Roxburgh, Matthias Ruebner, Stuart G Salfinger, Spinder Samra, Minouk J Schoemaker, Hans-Peter Sinn, Gabe S Sonke, Linda Steele, Colin J R Stewart, Aline Talhouk, Adeline Tan, Christopher M Tarney, Sarah E Taylor, Koen K Van de Vijver, Maaike A van der Aa, Toon Van Gorp, Els Van Nieuwenhuysen, Lilian Van-Wagensveld, Andrea E Wahner-Hendrickson, Christina Walter, Chen Wang, Julia Welz, Nicolas Wentzensen, Lynne R Wilkens, Stacey J Winham, Boris Winterhoff, Michael S Anglesio, Andrew Berchuck, Francisco J Candido Dos Reis, Paul A Cohen, Thomas P Conrads, Philip Crowe, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Simon A Gayther, Marc T Goodman, Jacek Gronwald, Holly R Harris, Florian Heitz, Hugo M Horlings, Beth Y Karlan, Linda E Kelemen, G Larry Maxwell, Usha Menon, Francesmary Modugno, Susan L Neuhausen, Joellen M Schildkraut, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Ignace Vergote, Anna H Wu, James D Brenton, Paul D P Pharoah, Celeste Leigh Pearce, Malcolm C Pike, Ellen L Goode, Susan J Ramus, Martin Köbel, Brad H Nelson, Anna DeFazio, Michael L Friedlander, David D L Bowtell, Dale W Garsed.
      BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience poor outcomes. In a large HGSC cohort (n = 1389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), residual disease after primary surgery has limited prognostic effect in gBRCApv-carriers compared to non-carriers, and prognostic outcomes differ based on the mutation location within functional domains of the BRCA genes. Multi-omic profiling is performed on 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival ( ≤ 3 years, n = 42). Patients with BRCA2-deficient HGSC and loss of NF1 survive twice as long as those without NF1 loss, whereas PIK3CA, RAD21 and MYC amplification define BRCA2-deficient HGSC with exceptionally short survival. Patients with BRCA1-deficient HGSC and a more elevated HRD score survive significantly longer. BRCA1-deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.
    DOI:  https://doi.org/10.1038/s41467-026-71134-3
  2. Int Rev Cell Mol Biol. 2026 ;pii: S1937-6448(26)00028-6. [Epub ahead of print]400 xiii-xvii
    Epigenetic regulation of cancer.
    Sheila Spada, Lorenzo Galluzzi.
      
    DOI:  https://doi.org/10.1016/S1937-6448(26)00028-6
  3. Fam Cancer. 2026 Mar 31. pii: 36. [Epub ahead of print]25(2):
    Hereditary gynecological cancer management in women with Lynch syndrome: a survey across Europe.
    ERN GENTURIS Survey Group
      
    Keywords:  Cancer genetics; Guidelines; Gynecological cancer; Hereditary cancer; Lynch syndrome; Multidisciplinary care
    DOI:  https://doi.org/10.1007/s10689-026-00546-3
  4. Eur J Cancer. 2026 Mar 24. pii: S0959-8049(26)00479-X. [Epub ahead of print]239 116699
    Integrating liquid biopsies and artificial intelligence for early cancer detection: A systematic review and meta-analysis.
    Panagiotis Filis, Georgios Markozannes, Dimitrios Salgkamis, Nikos Tsiknakis, Ioannis Zerdes, Eirini Pagkalidou, Maria Manou, Nikolaos Filis, Andri Papakonstantinou, Dimitrios Mavroudis, Alexios Matikas, Konstantinos K Tsilidis, Theodoros Foukakis.
       INTRODUCTION: The latest generation of liquid biopsies incorporates multi-omic features, including genomics, methylomics, and fragmentomics. Machine learning (ML) approaches have been proposed to synthesize these complex biological data for the development of diagnostic classifiers. This study aims to evaluate the integration of ML with circulating cell-free DNA (cfDNA) analysis for early cancer detection.
    METHODS: Medline, Embase, Cochrane, and Web of Science were searched in July 2025. Eligible studies combined ML and cfDNA features to distinguish cancer patients (stages I-III) from non-cancer controls. Summary diagnostic performance metrics and their 95% confidence intervals (CI) were calculated.
    RESULTS: The study included 109 articles permitting analyses for lung (n = 34), liver (n = 29), colorectal (n = 28), pancreatic (n = 16), breast (n = 17), esophageal (n = 12), ovarian (n = 13), gastric (n = 9), head and neck (n = 4), and mixed (n = 27) cancer types. Specificity was consistently high across all tumor types and stages (94%-99%). Sensitivity ranged from 72% to 92% for stage I-III, 44-91% for stage I, 71-98% for stage II and 83-99% for stage III. In the pooled study population, neural networks (90%, 95% CI: 81%-95%), random forest (86%, 95% CI: 77%-92%) and heterogeneous ensemble learning (85%, 95% CI: 79%-89%) demonstrated the highest sensitivity. The stratified analysis by classifier feature revealed 86% (95% CI: 80%-90%) sensitivity for fragmentation and 81% (95% CI: 76%-85%) for methylation, with 92%-96% specificity.
    CONCLUSION: ML and cfDNA profiling show potential for early cancer detection, with ensemble methods, neural networks and random forests achieving the best overall performance. Fragmentomic features provide the highest sensitivity.
    Keywords:  Artificial intelligence; CfDNA; Diagnosis; Early-stage cancer; Liquid biopsy
    DOI:  https://doi.org/10.1016/j.ejca.2026.116699
  5. Br J Cancer. 2026 Mar 30.
    Natural menopause, menarche and breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers: a Mendelian randomization analysis.
    EMBRACE
       BACKGROUND: The influence of age at menarche (AAM) and age at natural menopause (ANM) on breast cancer (BC) risk in BRCA1 and BRCA2 germline pathogenic variant (PV) carriers is uncertain. Observational studies are prone to bias and have limited statistical power. Mendelian randomization (MR) minimises bias and may be used to examine causal effects.
    METHODS: Two-sample and age-specific MR analyses for BC were performed. For AAM, two-sample multivariable MR and mediation analyses to account for the confounding effect of body mass index (BMI), were undertaken.
    RESULTS: Genetic scores for ANM and AAM predicted the respective traits in PV carriers. Inverse-variance weighted hazard ratios (HR) for genetically predicted ANM per-year were HR = 0.99 (95%CI:0.97-1.01, p = 0.45) and HR = 1.04 (95% CI:1.01-1.06, p = 0.003) for BRCA1 and BRCA2 PV carriers, respectively. After adjusting for genetic associations with BMI, AAM per-year on BC risk were HR = 0.90 (95%CI:0.83-0.98, p = 0.01) and HR = 0.95 (95%CI:0.86-1.04, p = 0.26) for BRCA1 and BRCA2 carriers, respectively, consistent with a protective effect of later AAM.
    DISCUSSION: MR analyses support causal associations between ANM and BC risk in BRCA2, but not BRCA1, and between AAM and BC risk in BRCA1 and BRCA2 PV carriers. These results may aid risk prediction models and genetic counselling of carriers.
    DOI:  https://doi.org/10.1038/s41416-026-03365-6
  6. Surg Oncol Clin N Am. 2026 04;pii: S1055-3207(25)00107-3. [Epub ahead of print]35(2): 399-414
    Utility of Circulating Tumor DNA-Based Liquid Biopsies in Patients with Cancer Receiving Immunotherapy.
    Maria Fernanda Teixeira, Nicole Fahmy, Pashtoon Murtaza Kasi.
      Liquid biopsies offer a promising, noninvasive approach for monitoring and predicting responses to immunotherapy across multiple solid tumors. For the most part these are circulating tumor DNA (ctDNA) based assays. Here, we discuss the biological basis, clinical evidence, and potential applications of different types of ctDNA assays in tracking tumor dynamics, distinguishing pseudoprogression, and assessing minimal residual disease. We explore the current limitations, assay variability, and future directions, including integration with other biomarkers and real-world clinical trials aimed at validating ctDNA as a routine tool in precision immuno-oncology.
    Keywords:  Circulating tumor DNA; Circulating tumor cells; Immune checkpoint inhibitors; Immunotherapy biomarkers; Liquid biopsy; Minimal residual disease; Pseudopogression; ctDNA
    DOI:  https://doi.org/10.1016/j.soc.2025.12.010
  7. Nat Cancer. 2026 Apr 03.
    Single-cell and spatial profiling in cancer biology and clinical oncology.
    Chris J Frangieh, Joy Linyue Fan, Johannes C Melms, Parin Shah, Elham Azizi, Benjamin Izar.
      Multiple single-cell and spatial genomics tools have transformed our ability to deconvolve intricate diseases, including cancer. Analysis of complex, multimodal data has provided insights into genomics, cellular states and interactions in tumor ecosystems, enabling the dissection of salient biology and expanding our understanding of drug response, resistance and target discovery. However, several challenges remain before these methods can achieve their full clinical potential. Here, we discuss opportunities, barriers and potential solutions, including sample acquisition and preservation approaches, profiling methods and analytical tools for heterogeneous populations, and we provide recommendations for robust, reproducible use of these technologies in clinical settings.
    DOI:  https://doi.org/10.1038/s43018-026-01142-1
  8. J Natl Cancer Inst. 2026 Mar 30. pii: djag100. [Epub ahead of print]
    Measuring and defining screening benefit in a new era of cancer early detection.
    Ruth Etzioni, Kemal Gogebakan, Roman Gulati, Lukas Owens, Jane Lange, Larry Kessler, Robert Smith, Deborah Schrag, Hilary A Robbins.
      We are at a watershed moment in the history of early cancer detection in which many novel tests are poised to become available for population screening. An ongoing debate concerns how to properly evaluate these tests and specifically whether a shorter-term, incidence-based outcome might substitute for cancer mortality as an endpoint in randomized trials of screening test efficacy. An incidence-based endpoint promises to reduce time and resources, but there is no framework for how studies using this endpoint should report results and how they should be interpreted in terms of clinical utility. We consider whether publication of incidence-based results ahead of any mortality results could result in adoption of new screening tests ahead of reliable mortality results becoming available. We argue that guardrails are needed for this scenario, including standards for conduct and reporting of trials with incidence-based endpoints to assure valid interpretation of clinical utility. For example, information regarding the type and timing of tests used for diagnostic workup in screen and control groups will be needed. Clinicians and policy makers will need to determine acceptable measurements and magnitudes of this modified measure of test efficacy. The roles of incidence-based and mortality-based endpoints in determining practice standards will need to be defined, along with specifications for permissible adjunct evidence, such as modeling studies and real-world data. As screening trials for new multi-cancer tests will soon begin to report incidence-based results, resolution of these questions is a matter of urgency.
    DOI:  https://doi.org/10.1093/jnci/djag100
  9. Front Oncol. 2026 ;16 1770012
    Clinical impact of clonal hematopoiesis on patients with solid tumors: a systematic review and meta-analysis.
    Vlad M Croitoru, Adina Turcu-Stiolica, Adina Emilia Croitoru, Doru Paul, Razvan Iacob, Alina Daniela Tanase, Adrian Saftoiu, Irina Sandra, Cristiana Tanase, Irina M Croitoru-Cazacu.
       Introduction: Clonal hematopoiesis (CH) is a common age-related phenomenon associated with an increased risk of hematologic malignancies and cardiovascular disease. Its prognostic significance in patients with solid tumors remains unclear. The aim of this meta-analysis was to evaluate the association between CH and clinical outcomes, including overall survival (OS), progression-free survival (PFS), cardiovascular events, and all-cause mortality in patients with solid tumors.
    Methods: We conducted a meta-analysis according to PRISMA guidelines, including 21 studies comprising 4845 patients with CH and 63557 patients without CH. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals were pooled using random-effects or fixed-effects models as appropriate, based on assessments of between-study heterogeneity.
    Results: CH was not significantly associated with OS in patients with solid tumors (HR: 1.10, 95% CI: 0.92-1.32, p = 0.30). The pooled analysis using a random-effects model suggested a trend toward improved PFS in patients with CH compared with those without CH, although statistical significance was not reached (HR: 0.83, 95% CI: 0.67-1.02, p = 0.08). However, CH was associated with an increased mortality in patients with solid tumors, with nearly a twofold higher risk compared to those without CH (OR = 1.70, 95% CI: 1.34-2.16, p < 0.00001). Furthermore, CH was significantly associated with an increased risk of cardiovascular events (OR = 2.75, 95% CI: 1.38 to 5.47, p = 0.004).
    Conclusion: Our meta-analysis indicated that CH mutations have a prognostic value and are associated with a clinically meaningful increased risk of overall mortality and cardiovascular events in patients with solid tumors.
    Keywords:  CHIP; cardiovascular events; clonal hematopoiesis; prognosis; solid tumors; survival
    DOI:  https://doi.org/10.3389/fonc.2026.1770012
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