bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–07–12
twelve papers selected by
Lara Paracchini, Humanitas Research
  1. Focus on BRCA1 and BRCA2.
  2. A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing.
  3. Role of Genetics in Gynecologic Malignancies.
  4. Liquid biopsy for early cancer detection in hereditary cancer syndromes: current evidence.
  5. Daily briefing: Three decades of Dolly.
  6. Polygenic risk scores in cancer.
  7. Role of Genetics in Gastric Malignancy: Screening, Prevention and Treatment.
  8. Moving beyond the neutral-Darwinian dichotomy to inform precision oncology.
  9. Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.
  10. Circulating tumor DNA in early breast cancer: Evidence, challenges, next steps.
  11. Pancreatic Cancer: Genetics, Screening, Prevention, and Treatment.
  12. A Lynch syndrome patient with multiple cancers who was found to have a novel pathogenic variant generating aberrant splicing of MLH1.
  1. Nat Genet. 2026 Jul 10.
    Focus on BRCA1 and BRCA2.
      
    DOI:  https://doi.org/10.1038/s41588-026-02690-z
  2. Sci Adv. 2026 Jul 10. 12(28): eady9432
    A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing.
    Haichao Wang, Paulius D Mennea, Grainne McAndrew, Ozge Sonmezler, Dmitry S Shcherbo, Emma-Jane Ditter, Sarah Østrup Jensen, Alessandra I G Buma, Christopher G Smith, Zhao Cheng, Clare Harris, Rosalind J Cutts, Sarah Hrebien, Philip A J Crosbie, Pippa G Corrie, Michel M van den Heuvel, Amit Roshan, Frank McCaughan, Robert C Rintoul, Florian Markowetz, Tommy Kaplan, Wendy N Cooper, Hui Zhao, Nitzan Rosenfeld.
      Cell-free DNA (cfDNA) in body fluids enables noninvasive cancer detection. Multifeature artificial intelligence (AI) can improve sensitivity by integrating diverse biomarkers when cancer signals are sparse. Tumor-informed assays that rely on mutations have limited practicality for early cancer detection. Emerging fragmentomic and epigenetic features underpin tumor-naive approaches to screening for individuals with low tumor burden. Here, we designed UNITE-a universal cfDNA feature ensemble framework that provides scalable cancer detection methods based on "genomic bin-fragment length" matrices derived from shallow whole-genome sequencing (sWGS) data at 0.1× depth. Using sWGS data from 2063 plasma samples (631 controls and 1432 cases from 26 cancer types), we systematically evaluated both XGBoost (UNITE-XGB) and convolutional neural networks (UNITE-CNN) across multiple feature spaces and cancer stages. In stage I-II cancer, UNITE-XGB and UNITE-CNN achieved 31 and 21% sensitivity, respectively, at 95% specificity. These findings provide roadmaps for developing multifeature AI beyond plasma biopsies.
    DOI:  https://doi.org/10.1126/sciadv.ady9432
  3. Surg Clin North Am. 2026 Aug;pii: S0039-6109(26)00032-0. [Epub ahead of print]106(4): 585-602
    Role of Genetics in Gynecologic Malignancies.
    Corbyn M Nchako, Kara C Long, Ying L Liu, Yukio Sonoda.
      Advances in cancer genomics have transformed the prevention, classification, and management of gynecologic malignancies. Germline and somatic genetic alterations now inform hereditary cancer risk assessment, molecular tumor classification, and selection of targeted and immune-based therapies. Syndromes such as BRCA-associated hereditary breast and ovarian cancer and Lynch syndrome guide surveillance, cascade testing, and risk-reducing surgery. Molecular frameworks, including The Cancer Genome Atlas classification in endometrial cancer, refine prognosis and treatment intensity. Biomarker-driven therapies-such as poly (ADP-ribose) polymerase inhibitors, immune checkpoint inhibitors, and HER2-directed agents-have become integral across disease stages.
    Keywords:  BRCA; Endometrial carcinoma; Mismatch repair; Molecular subtype; Risk-reducing; Tubo-ovarian
    DOI:  https://doi.org/10.1016/j.suc.2026.03.004
  4. Crit Rev Oncol Hematol. 2026 Jul 07. pii: S1040-8428(26)00362-8. [Epub ahead of print] 105475
    Liquid biopsy for early cancer detection in hereditary cancer syndromes: current evidence.
    Michaela Kuhlen, Maximilian Schmut, Markus Metzle, Rainer Claus.
      Hereditary cancer predisposition syndromes (CPS) confer high lifetime cancer risks with early onset and diverse tumor spectra, posing challenges for current intensive, organ-specific surveillance methods that carry risks of interval cancers, radiation exposure, and patient burden. Here we synthesize evidence on cell-free DNA (cfDNA)-based liquid biopsy approaches-including methylation, fragmentomics, copy-number, and mutation analyses-as minimally invasive adjuncts for early cancer detection in CPS. Data, primarily from Li-Fraumeni syndrome, Lynch syndrome, and neurofibromatosis type 1, demonstrate promising diagnostic performance, particularly with multimodal cfDNA assays that improve detection sensitivity and specificity. However, no randomized trials have yet confirmed clinical benefit. Ongoing studies aim to clarify optimal testing strategies, psychosocial impact, and cost-effectiveness. These findings suggest that cfDNA liquid biopsy holds potential to complement existing surveillance in hereditary cancer syndromes, but further validation is required before routine clinical implementation.
    Keywords:  Li-Fraumeni syndrome; Liquid biopsy; cell-free DNA; hereditary cancer syndromes; multi-cancer early detection
    DOI:  https://doi.org/10.1016/j.critrevonc.2026.105475
  5. Nature. 2026 Jul 07.
    Daily briefing: Three decades of Dolly.
    Flora Graham.
      
    DOI:  https://doi.org/10.1038/d41586-026-02136-w
  6. Med Genet. 2026 Jul;38(3): 187-198
    Polygenic risk scores in cancer.
    Anja Tüchler, Laura Grohs, Alexander Volk, Stefan Aretz.
      Polygenic risk scores (PRS) have emerged as a powerful tool to refine cancer risk prediction beyond age, family history, and modifiable environmental risk factors, enabling individualized prevention and early detection strategies. Evidence from breast, colorectal, and prostate cancer demonstrates that PRS significantly improve risk stratification in both sporadic and hereditary settings and can modify penetrance of pathogenic germline variants. Integrating PRS into multifactorial models such as CanRisk enhances predictive accuracy and supports risk-adapted preventive approaches. While implementation studies show feasibility, prospective validation and standardization as well as ancestry-specific calibration remain key challenges for clinical translation.
    Keywords:  Tumour predisposition syndromes; genetic diagnostics; prevention; risk stratification; surveillance
    DOI:  https://doi.org/10.1515/medgen-2026-3011
  7. Surg Clin North Am. 2026 Aug;pii: S0039-6109(26)00034-4. [Epub ahead of print]106(4): 519-531
    Role of Genetics in Gastric Malignancy: Screening, Prevention and Treatment.
    Rui Zheng-Pywell, Perry Shen.
      There are 3 known hereditary gastric cancers that contribute to 1% to 3% of all gastric malignancies: hereditary diffuse gastric cancer, gastric adenocarcinoma and proximal polyposis of the stomach, and familial intestinal gastric cancer. Additional hereditary cancer syndromes also contribute to increased lifetime risks of gastric malignancies: hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers, Li-Fraumeni, and juvenile polyposis syndrome. Germline mutations in DNA damage repair genes may be contributing to the pathogenesis of gastric cancer and may be a target for future therapeutic modalities.
    Keywords:  Hereditary gastric cancer; Heritable genetic syndromes; Screening
    DOI:  https://doi.org/10.1016/j.suc.2026.03.006
  8. NPJ Precis Oncol. 2026 Jul 10.
    Moving beyond the neutral-Darwinian dichotomy to inform precision oncology.
    Amit Sud, Richard S Houlston.
      Current methods for distinguishing neutral from selection-driven tumour evolution rely on assumptions frequently violated in clinical samples. We argue that tumour evolution is not a binary state, but a dynamic continuum shaped by genetic and non-genetic heterogeneity, spatial constraints, microenvironmental pressures and therapeutic bottlenecks. Refining evolutionary inference through integrative, longitudinal and spatially resolved analyses will be essential to align these models with therapeutic decision-making in precision oncology.
    DOI:  https://doi.org/10.1038/s41698-026-01606-8
  9. Ann Transl Med. 2026 Jun 30. 14(3): 34
    Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.
    Ankita Dhenge, Rohan Kulkarni.
      Aging is associated with organ and tissue function deterioration and consequent increased risk of disease occurrence and mortality. Recent scientific advancements have succeeded in increasing the human life span and attempts are being made to enhance the longevity further. This stretched longevity exposes the organism to increased cellular stress and accumulation of DNA damage. Mutations in leukemia-associated driver oncogenes like DNMT3A, TET2, ASXL1, TP53, PPM1D, SF3B1, SRSF2, and IDH1/2, provide selective growth advantage to the mutated clones over normal hematopoietic stem cells (HSCs). Altered bone marrow (BM) microenvironment and increased pro-inflammatory milieu further accelerates the clonal expansion and eventually reduces the hematopoietic heterogeneity. Significant increase in clonal hematopoiesis with more than two percent of peripheral blood cells arising from single hematopoietic clone is termed as clonal hematopoiesis of indeterminate potential (CHIP). CHIP is increasingly recognized as an age-associated risk factor linked to cardiovascular and neurological disorders. While epidemiological and experimental studies suggest mechanistic involvement of inflammation, current human evidence primarily supports risk association rather than definitive causality, which may vary across mutation types. Here, we have discussed the intrinsic and extrinsic changes occurring in the hematopoietic system and its role in enhancing the clonal expansion during aging. We have further discussed the role of CHIP in various diseases and diagnostic tools being currently used for CHIP diagnosis. Finally, we also discuss the current CHIP management strategies and global status of CHIP related research. Thus, the emerging CHIP-cantered research and new strategies to impede CHIP progression can play a critical role in the development of effective therapeutic strategies for managing age-related obnoxious disorders.
    Keywords:  Aging; aging related disorders; clonal hematopoiesis of indeterminate potential (CHIP); hematopoiesis; inflammaging
    DOI:  https://doi.org/10.21037/atm-2026-1-0030
  10. Cancer. 2026 Jul 15. 132(14): e70521
    Circulating tumor DNA in early breast cancer: Evidence, challenges, next steps.
    Serena Di Cosimo, Valentina Appierto, Carolina Reduzzi, Loris De Cecco, Carmine Valenza, Lorenzo Gerratana, Elisa Agostinetto, Antonio Llombart-Cussac, Michail Ignatiadis, Javier Cortes, Massimo Cristofanilli, Nicola Fusco, Giuseppe Curigliano, Giancarlo Pruneri.
      Circulating tumor DNA (ctDNA) is a tumor-derived, circulating bioanalyte that can be detected in blood using minimally invasive, blood-based biomarker procedures and has prognostic value in early breast cancer. Quantitative features of ctDNA, including baseline detectability and levels, have shown prognostic potential in early breast cancer by reflecting tumor burden and biologic aggressiveness, thereby supporting risk stratification. Post-treatment ctDNA detection may identify minimal residual disease and can precede radiologic or symptomatic recurrence by several months to years. Nevertheless, ctDNA has not yet been adopted in routine clinical practice in early breast cancer, partly because of biologic constraints, including low and heterogeneous tumor DNA shedding, as well as pre-analytical and analytical variability that can affect testing sensitivity. Ongoing efforts are focused on methodological standardization and clarification of the clinically actionable context. This narrative review examines the challenges in applying ctDNA to early breast cancer, spanning patient selection, sampling logistics, specimen handling, assay performance, and sources of assay failure. The authors outline determinants of ctDNA measurement that restrict the proportion of evaluable patients and limit translation to clinical practice and then summarize evidence supporting ctDNA for early response monitoring during neoadjuvant therapy, postoperative minimal residual disease detection, and longitudinal molecular surveillance. Finally, ctDNA-guided therapeutic interception strategies and emerging multimodal cell-free DNA approaches are discussed.
    Keywords:  circulating tumor DNA; early breast cancer; minimal residual disease (MRD); precision oncology; surveillance
    DOI:  https://doi.org/10.1002/cncr.70521
  11. Surg Clin North Am. 2026 Aug;pii: S0039-6109(26)00037-X. [Epub ahead of print]106(4): 533-553
    Pancreatic Cancer: Genetics, Screening, Prevention, and Treatment.
    Sami O Abul-Khoudoud, Jeffrey M Hardacre.
      Pancreatic cancer is a highly lethal malignancy with an overall 5-year survival rate of just 13%, and its most common histologic subtype, pancreatic ductal adenocarcinoma (PDAC), carries an even poorer prognosis. Its aggressive nature is driven by complex genetic, epigenetic, and microenvironmental alterations. Key driver mutations in Kirsten rat sarcoma, cyclin-dependent kinase inhibitor 2A, TP53, and SMAD4 promote tumorigenesis, genomic instability, and resistance to therapy. Advances in molecular profiling have improved the understanding of PDAC biology, identifying actionable mutations and therapeutic targets. Despite progress, effective targeted therapies remain limited, and early metastasis continues to hinder outcomes. Ongoing research aims to refine patient selection and optimize treatments.
    Keywords:  Familial pancreatic cancer; Genetics; Pancreatic cancer; Screening; Targeted therapy
    DOI:  https://doi.org/10.1016/j.suc.2026.03.009
  12. Jpn J Clin Oncol. 2026 Jul 06. pii: hyag101. [Epub ahead of print]
    A Lynch syndrome patient with multiple cancers who was found to have a novel pathogenic variant generating aberrant splicing of MLH1.
    Ayumi Abe, Hidetaka Eguchi, Kimio Matsumura, Yudai Fukui, Kosuke Hiramatsu, Takeshi Fujii, Masako Ikemura, Gaku Kuge, Hiroya Kuroyanagi, Yasushi Okazaki, Masami Arai.
      Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by inactivating germline variants in DNA mismatch repair genes. Here, we describe a woman who developed colorectal, gastric, and endometrial cancers and was found to have a rare missense variant, MLH1:c.545G > T/p.Arg182Met. The variant, which was located at the last nucleotide of MLH1exon 6, was initially reported by a clinical testing laboratory as being a variant of uncertain significance. In silico analyses predicted that it would cause splicing aberration, and reverse-transcription polymerase chain reaction analysis of total RNA from the patient's peripheral blood cells identified an aberrant MLH1 transcript that skipped the entire exon 6 and caused generation of a premature stop codon (p.Glu153Phefs*8). In accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, we reclassified the variant as likely pathogenic. Further additional analysis enabled carrier diagnosis in the patient's relatives. Genetics summary Disorder: Lynch syndrome Ethnicity of the patient: Japanese Gene: MLH1 (19 exons) GenBank accession number: NM_000249.4 Chromosomal assignment: 3p21.3 Type of DNA variant: a germline splice aberration variant Mutation: c.545G > T in exon 6 of MLH1 Methods of mutation detection: PCR-sequencing, RT-PCR.
    Keywords:   MLH1 ; Lynch syndrome; RT-PCR; splice aberration variant
    DOI:  https://doi.org/10.1093/jjco/hyag101
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